US11897857B2 - Isotopically-stabilized tetronimide compounds - Google Patents
Isotopically-stabilized tetronimide compounds Download PDFInfo
- Publication number
- US11897857B2 US11897857B2 US17/119,602 US202017119602A US11897857B2 US 11897857 B2 US11897857 B2 US 11897857B2 US 202017119602 A US202017119602 A US 202017119602A US 11897857 B2 US11897857 B2 US 11897857B2
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- US
- United States
- Prior art keywords
- amino
- oxo
- dihydrofuran
- phenylmethanesulfonate
- phenyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 321
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
- 201000010099 disease Diseases 0.000 claims abstract description 21
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 9
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 6
- 229910052805 deuterium Inorganic materials 0.000 claims description 37
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 27
- 239000012453 solvate Substances 0.000 claims description 26
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 19
- 229940002612 prodrug Drugs 0.000 claims description 19
- 239000000651 prodrug Substances 0.000 claims description 19
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- 239000002207 metabolite Substances 0.000 claims description 18
- 230000000155 isotopic effect Effects 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 10
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 10
- 150000001975 deuterium Chemical group 0.000 claims description 10
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 9
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 230000023555 blood coagulation Effects 0.000 claims description 7
- 230000003612 virological effect Effects 0.000 claims description 7
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 5
- PBYZWRBKXRHUSG-LMOOGUKRSA-N [(5R)-2-amino-5-(3-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=CC=C1)Cl)F)N)([2H])[2H] PBYZWRBKXRHUSG-LMOOGUKRSA-N 0.000 claims description 5
- RFXJFUNFUREASK-TVLGPKEFSA-N [(5R)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] RFXJFUNFUREASK-TVLGPKEFSA-N 0.000 claims description 5
- JSENTRJIUXBCNY-TVLGPKEFSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] JSENTRJIUXBCNY-TVLGPKEFSA-N 0.000 claims description 5
- XITRFEDNNGVURT-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(3,4-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=C(C=C1)Cl)Cl)N)([2H])[2H] XITRFEDNNGVURT-LMOOGUKRSA-N 0.000 claims description 5
- PBYZWRBKXRHUSG-SWMWQOICSA-N [(5S)-2-amino-5-(3-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=CC=C1)Cl)F)N)([2H])[2H] PBYZWRBKXRHUSG-SWMWQOICSA-N 0.000 claims description 5
- RFXJFUNFUREASK-BCYJYSMKSA-N [(5S)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] RFXJFUNFUREASK-BCYJYSMKSA-N 0.000 claims description 5
- JSENTRJIUXBCNY-BCYJYSMKSA-N [(5S)-2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] JSENTRJIUXBCNY-BCYJYSMKSA-N 0.000 claims description 5
- XITRFEDNNGVURT-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(3,4-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=C(C=C1)Cl)Cl)N)([2H])[2H] XITRFEDNNGVURT-SWMWQOICSA-N 0.000 claims description 5
- RFXJFUNFUREASK-PZHCDCHGSA-N [2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] RFXJFUNFUREASK-PZHCDCHGSA-N 0.000 claims description 5
- JSENTRJIUXBCNY-OIDIABAASA-N [2-amino-5-deuterio-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N)([2H])[2H] JSENTRJIUXBCNY-OIDIABAASA-N 0.000 claims description 5
- JSENTRJIUXBCNY-PZHCDCHGSA-N [2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] JSENTRJIUXBCNY-PZHCDCHGSA-N 0.000 claims description 5
- XITRFEDNNGVURT-SMNVOWQRSA-N [2-amino-5-deuterio-5-(3,4-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=C(C=C1)Cl)Cl)N)([2H])[2H] XITRFEDNNGVURT-SMNVOWQRSA-N 0.000 claims description 5
- JSENTRJIUXBCNY-LJTPDOSZSA-N [5-deuterio-2-(dideuterioamino)-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-LJTPDOSZSA-N 0.000 claims description 5
- 208000015294 blood coagulation disease Diseases 0.000 claims description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 5
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 5
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 5
- RGIFNCKGVFMIBW-QDQVUVIPSA-N methyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]-2-fluorobenzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC(=C(C(=O)OC)C=C1)F)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 RGIFNCKGVFMIBW-QDQVUVIPSA-N 0.000 claims description 5
- LHPXMEBVGVXZCU-FAODQTPUSA-N methyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)OC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 LHPXMEBVGVXZCU-FAODQTPUSA-N 0.000 claims description 5
- RGIFNCKGVFMIBW-PYQSMLQDSA-N methyl 4-[5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]-2-fluorobenzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC(=C(C(=O)OC)C=C1)F)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 RGIFNCKGVFMIBW-PYQSMLQDSA-N 0.000 claims description 5
- LHPXMEBVGVXZCU-CXVUVLKYSA-N methyl 4-[5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)OC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 LHPXMEBVGVXZCU-CXVUVLKYSA-N 0.000 claims description 5
- 150000003536 tetrazoles Chemical class 0.000 claims description 5
- 150000003852 triazoles Chemical class 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000006738 (C6-C20) heteroaryl group Chemical group 0.000 claims description 4
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 claims description 4
- JSENTRJIUXBCNY-SCCBWLMSSA-N [2-(dideuterioamino)-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] (2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])CS(=O)(=O)OC1=C(OC(C1=O)C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N([2H])[2H] JSENTRJIUXBCNY-SCCBWLMSSA-N 0.000 claims description 4
- JSENTRJIUXBCNY-WWIFOTOZSA-N [2-(dideuterioamino)-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] phenylmethanesulfonate Chemical compound C1(=CC=CC=C1)CS(=O)(=O)OC1=C(OC(C1=O)C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N([2H])[2H] JSENTRJIUXBCNY-WWIFOTOZSA-N 0.000 claims description 4
- JSENTRJIUXBCNY-LQHBDRBESA-N [2-(dideuterioamino)-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] (2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])CS(=O)(=O)OC1=C(OC(C1=O)C1=CC=C(C=C1)C(F)(F)F)N([2H])[2H] JSENTRJIUXBCNY-LQHBDRBESA-N 0.000 claims description 4
- JSENTRJIUXBCNY-ZSJDYOACSA-N [2-(dideuterioamino)-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] phenylmethanesulfonate Chemical compound C1(=CC=CC=C1)CS(=O)(=O)OC1=C(OC(C1=O)C1=CC=C(C=C1)C(F)(F)F)N([2H])[2H] JSENTRJIUXBCNY-ZSJDYOACSA-N 0.000 claims description 4
- PBYZWRBKXRHUSG-SMNVOWQRSA-N [2-amino-5-(3-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=CC=C1)Cl)F)N)([2H])[2H] PBYZWRBKXRHUSG-SMNVOWQRSA-N 0.000 claims description 4
- PUQUKIZPSCRUKV-LJTPDOSZSA-N [2-amino-5-deuterio-5-[4-(dideuteriocarbamoyl)phenyl]-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(N([2H])[2H])=O)N)([2H])[2H] PUQUKIZPSCRUKV-LJTPDOSZSA-N 0.000 claims description 4
- WCZBUQIZTSIQFE-UHFFFAOYSA-N furan;thiophene Chemical compound C=1C=COC=1.C=1C=CSC=1 WCZBUQIZTSIQFE-UHFFFAOYSA-N 0.000 claims description 4
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- CMGNFILMNHGISN-UHFFFAOYSA-N oxadiazole;thiadiazole Chemical compound C1=CON=N1.C1=CSN=N1 CMGNFILMNHGISN-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- RBMNZNDOGRAYCO-WVYCSPNRSA-N (2-amino-5-deuterio-4-oxo-5-phenylfuran-3-yl) dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=CC=C1)N)([2H])[2H] RBMNZNDOGRAYCO-WVYCSPNRSA-N 0.000 claims description 3
- 208000005331 Hepatitis D Diseases 0.000 claims description 3
- 241000701806 Human papillomavirus Species 0.000 claims description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
- KCTOHJCNLJXFHH-GOOQESARSA-N NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] KCTOHJCNLJXFHH-GOOQESARSA-N 0.000 claims description 3
- NOUIBHNVHOFCKG-DGTQYHKXSA-N NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F NOUIBHNVHOFCKG-DGTQYHKXSA-N 0.000 claims description 3
- KCTOHJCNLJXFHH-FTEZPROFSA-N NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 KCTOHJCNLJXFHH-FTEZPROFSA-N 0.000 claims description 3
- NOUIBHNVHOFCKG-BJNJBBEASA-N NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F NOUIBHNVHOFCKG-BJNJBBEASA-N 0.000 claims description 3
- KCTOHJCNLJXFHH-HUYKZCAJSA-N NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 KCTOHJCNLJXFHH-HUYKZCAJSA-N 0.000 claims description 3
- NOUIBHNVHOFCKG-ZFTYOPGDSA-N NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F Chemical compound NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F NOUIBHNVHOFCKG-ZFTYOPGDSA-N 0.000 claims description 3
- KCTOHJCNLJXFHH-RHSFUWAESA-N NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 Chemical compound NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 KCTOHJCNLJXFHH-RHSFUWAESA-N 0.000 claims description 3
- ZUEYSOISQIRWHI-QEZZGCPKSA-N [(5R)-2-amino-5-(1,3-benzodioxol-5-yl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC2=C(OCO2)C=C1)N)([2H])[2H] ZUEYSOISQIRWHI-QEZZGCPKSA-N 0.000 claims description 3
- VNMMWJDNBNERJS-TVLGPKEFSA-N [(5R)-2-amino-5-(2-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1)Br)N)([2H])[2H] VNMMWJDNBNERJS-TVLGPKEFSA-N 0.000 claims description 3
- VVJQQPNTDSBJGO-LMOOGUKRSA-N [(5R)-2-amino-5-(2-chloro-3-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=CC=C1)F)Cl)N)([2H])[2H] VVJQQPNTDSBJGO-LMOOGUKRSA-N 0.000 claims description 3
- LBPGBBOUMNREPT-LMOOGUKRSA-N [(5R)-2-amino-5-(2-chloro-4-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=C(C=C1)F)Cl)N)([2H])[2H] LBPGBBOUMNREPT-LMOOGUKRSA-N 0.000 claims description 3
- KFIICSGBLRSJPA-LMOOGUKRSA-N [(5R)-2-amino-5-(2-chloro-5-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC(=C1)F)Cl)N)([2H])[2H] KFIICSGBLRSJPA-LMOOGUKRSA-N 0.000 claims description 3
- MDJJAEKJZSERFA-LMOOGUKRSA-N [(5R)-2-amino-5-(2-chloro-6-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1F)Cl)N)([2H])[2H] MDJJAEKJZSERFA-LMOOGUKRSA-N 0.000 claims description 3
- FOGWFWDJRVMWKA-TVLGPKEFSA-N [(5R)-2-amino-5-(2-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1)Cl)N)([2H])[2H] FOGWFWDJRVMWKA-TVLGPKEFSA-N 0.000 claims description 3
- MHLYYVLTOYRHRL-TVLGPKEFSA-N [(5R)-2-amino-5-(3-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC=C1)Br)N)([2H])[2H] MHLYYVLTOYRHRL-TVLGPKEFSA-N 0.000 claims description 3
- VLJVMMHJHOBTIG-LMOOGUKRSA-N [(5R)-2-amino-5-(3-chloro-4-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=C(C=C1)F)Cl)N)([2H])[2H] VLJVMMHJHOBTIG-LMOOGUKRSA-N 0.000 claims description 3
- RSTVETSPNBACFW-LMOOGUKRSA-N [(5R)-2-amino-5-(3-chloro-5-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC(=C1)F)Cl)N)([2H])[2H] RSTVETSPNBACFW-LMOOGUKRSA-N 0.000 claims description 3
- SDGJJRNVCOGVAG-TVLGPKEFSA-N [(5R)-2-amino-5-(3-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC=C1)Cl)N)([2H])[2H] SDGJJRNVCOGVAG-TVLGPKEFSA-N 0.000 claims description 3
- OZSTYEYYIZOGJR-FAODQTPUSA-N [(5R)-2-amino-5-(3-cyanophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC=C1)C#N)N)([2H])[2H] OZSTYEYYIZOGJR-FAODQTPUSA-N 0.000 claims description 3
- OTWZNPQDTYKBKE-TVLGPKEFSA-N [(5R)-2-amino-5-(4-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Br)N)([2H])[2H] OTWZNPQDTYKBKE-TVLGPKEFSA-N 0.000 claims description 3
- PUQUKIZPSCRUKV-TVLGPKEFSA-N [(5R)-2-amino-5-(4-carbamoylphenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(N)=O)N)([2H])[2H] PUQUKIZPSCRUKV-TVLGPKEFSA-N 0.000 claims description 3
- CSOJGNWXIRSATJ-LMOOGUKRSA-N [(5R)-2-amino-5-(4-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=C(C=C1)Cl)F)N)([2H])[2H] CSOJGNWXIRSATJ-LMOOGUKRSA-N 0.000 claims description 3
- UHJBGKUXTPVWDM-LMOOGUKRSA-N [(5R)-2-amino-5-(4-chloro-3-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=C(C=C1)Cl)F)N)([2H])[2H] UHJBGKUXTPVWDM-LMOOGUKRSA-N 0.000 claims description 3
- AIMVCVQVRLGLRH-SPTSOKAQSA-N [(5R)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuterio-2-methylpropane-1-sulfonate Chemical compound CC(C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H])C AIMVCVQVRLGLRH-SPTSOKAQSA-N 0.000 claims description 3
- XXJFDCICKAWHSZ-VSWIATKZSA-N [(5R)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuteriobutane-1-sulfonate Chemical compound C(CCC)(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] XXJFDCICKAWHSZ-VSWIATKZSA-N 0.000 claims description 3
- VCNOSHCOKRGAFH-ZLKPMISRSA-N [(5R)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuterioethanesulfonate Chemical compound C(C)(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] VCNOSHCOKRGAFH-ZLKPMISRSA-N 0.000 claims description 3
- OWVBFOSPAPHJPY-FYESUYBQSA-N [(5R)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuteriopropane-1-sulfonate Chemical compound C(CC)(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] OWVBFOSPAPHJPY-FYESUYBQSA-N 0.000 claims description 3
- SYCCMZVSTUCIHF-NILQLGHYSA-N [(5R)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 2-deuteriopropane-2-sulfonate Chemical compound CC(C)(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)[2H] SYCCMZVSTUCIHF-NILQLGHYSA-N 0.000 claims description 3
- WRYVLBKLGDJEPA-SRSCGJFZSA-N [(5R)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] benzenesulfonate Chemical compound C1(=CC=CC=C1)S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Cl)N WRYVLBKLGDJEPA-SRSCGJFZSA-N 0.000 claims description 3
- AFTCLAGEFNWDOX-FJKVMUFJSA-N [(5R)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] trideuteriomethanesulfonate Chemical compound C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])([2H])[2H] AFTCLAGEFNWDOX-FJKVMUFJSA-N 0.000 claims description 3
- ULTBFGINDWYOAO-FAODQTPUSA-N [(5R)-2-amino-5-(4-cyanophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C#N)N)([2H])[2H] ULTBFGINDWYOAO-FAODQTPUSA-N 0.000 claims description 3
- FXUAIYVNGBMTBB-LMOOGUKRSA-N [(5R)-2-amino-5-(5-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC(=C1)Cl)F)N)([2H])[2H] FXUAIYVNGBMTBB-LMOOGUKRSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-KRQPZEPOSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N)([2H])[2H] JSENTRJIUXBCNY-KRQPZEPOSA-N 0.000 claims description 3
- CGQRROWINGCADB-TVLGPKEFSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[2-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1)C(F)(F)F)N)([2H])[2H] CGQRROWINGCADB-TVLGPKEFSA-N 0.000 claims description 3
- PLRFYKHCOKBGPL-TVLGPKEFSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[3-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC=C1)C(F)(F)F)N)([2H])[2H] PLRFYKHCOKBGPL-TVLGPKEFSA-N 0.000 claims description 3
- AAMMUKIEONIWFZ-AEIGJHGBSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[6-(trifluoromethyl)pyridin-3-yl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C=1C=NC(=CC=1)C(F)(F)F)N)([2H])[2H] AAMMUKIEONIWFZ-AEIGJHGBSA-N 0.000 claims description 3
- RBMNZNDOGRAYCO-YWIOKFLASA-N [(5R)-2-amino-5-deuterio-4-oxo-5-phenylfuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=CC=C1)N)([2H])[2H] RBMNZNDOGRAYCO-YWIOKFLASA-N 0.000 claims description 3
- YSMZUVFIILJEIO-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(2,2-difluoro-1,3-benzodioxol-5-yl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC2=C(OC(O2)(F)F)C=C1)N)([2H])[2H] YSMZUVFIILJEIO-LMOOGUKRSA-N 0.000 claims description 3
- RKSVAVTXWOUTKP-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(2,3-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=CC=C1)Cl)Cl)N)([2H])[2H] RKSVAVTXWOUTKP-LMOOGUKRSA-N 0.000 claims description 3
- UEIXZUNCVZXURR-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(2,3-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=CC=C1)F)F)N)([2H])[2H] UEIXZUNCVZXURR-LMOOGUKRSA-N 0.000 claims description 3
- UZMVSVRIMLYTFC-UQSZZEIXSA-N [(5R)-2-amino-5-deuterio-5-(2,3-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=CC=C1)OC)OC)N)([2H])[2H] UZMVSVRIMLYTFC-UQSZZEIXSA-N 0.000 claims description 3
- FSAGXOYHOPYBLM-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(2,4-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=C(C=C1)Cl)Cl)N)([2H])[2H] FSAGXOYHOPYBLM-LMOOGUKRSA-N 0.000 claims description 3
- MRANPYZDQRPVMQ-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(2,4-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=C(C=C1)F)F)N)([2H])[2H] MRANPYZDQRPVMQ-LMOOGUKRSA-N 0.000 claims description 3
- UTLRIETUSATVLU-UQSZZEIXSA-N [(5R)-2-amino-5-deuterio-5-(2,4-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=C(C=C1)OC)OC)N)([2H])[2H] UTLRIETUSATVLU-UQSZZEIXSA-N 0.000 claims description 3
- NRSDXXYHJSXZIM-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(2,5-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC(=C1)Cl)Cl)N)([2H])[2H] NRSDXXYHJSXZIM-LMOOGUKRSA-N 0.000 claims description 3
- ZINZHCFHUQQGOC-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(2,5-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC(=C1)F)F)N)([2H])[2H] ZINZHCFHUQQGOC-LMOOGUKRSA-N 0.000 claims description 3
- ABEXEQNVKLVRTN-UQSZZEIXSA-N [(5R)-2-amino-5-deuterio-5-(2,5-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC(=C1)OC)OC)N)([2H])[2H] ABEXEQNVKLVRTN-UQSZZEIXSA-N 0.000 claims description 3
- UXLGTLOXBAKPJN-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(2,6-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1F)F)N)([2H])[2H] UXLGTLOXBAKPJN-LMOOGUKRSA-N 0.000 claims description 3
- NWAYGVMPOGETRW-UQSZZEIXSA-N [(5R)-2-amino-5-deuterio-5-(2,6-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1OC)OC)N)([2H])[2H] NWAYGVMPOGETRW-UQSZZEIXSA-N 0.000 claims description 3
- RMXWGKXYBJIXBE-TVLGPKEFSA-N [(5R)-2-amino-5-deuterio-5-(2-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1)F)N)([2H])[2H] RMXWGKXYBJIXBE-TVLGPKEFSA-N 0.000 claims description 3
- YXFYSGOXEMVSMD-FAODQTPUSA-N [(5R)-2-amino-5-deuterio-5-(2-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1)OC)N)([2H])[2H] YXFYSGOXEMVSMD-FAODQTPUSA-N 0.000 claims description 3
- OEYDNENGPIRMQX-FAODQTPUSA-N [(5R)-2-amino-5-deuterio-5-(2-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C=CC=C1)C)N)([2H])[2H] OEYDNENGPIRMQX-FAODQTPUSA-N 0.000 claims description 3
- QRSZCGYMHKMZOG-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(3,4-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=C(C=C1)F)F)N)([2H])[2H] QRSZCGYMHKMZOG-LMOOGUKRSA-N 0.000 claims description 3
- ORZDSIAWTHZDNR-UQSZZEIXSA-N [(5R)-2-amino-5-deuterio-5-(3,4-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=C(C=C1)OC)OC)N)([2H])[2H] ORZDSIAWTHZDNR-UQSZZEIXSA-N 0.000 claims description 3
- TYLBFGJWPMBOSE-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(3,5-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC(=C1)Cl)Cl)N)([2H])[2H] TYLBFGJWPMBOSE-LMOOGUKRSA-N 0.000 claims description 3
- GCYOEKPCUFCJOL-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-5-(3,5-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC(=C1)F)F)N)([2H])[2H] GCYOEKPCUFCJOL-LMOOGUKRSA-N 0.000 claims description 3
- NNENVKFNMNCPJU-UQSZZEIXSA-N [(5R)-2-amino-5-deuterio-5-(3,5-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC(=C1)OC)OC)N)([2H])[2H] NNENVKFNMNCPJU-UQSZZEIXSA-N 0.000 claims description 3
- NHVBIMUJMMJGDO-TVLGPKEFSA-N [(5R)-2-amino-5-deuterio-5-(3-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC=C1)F)N)([2H])[2H] NHVBIMUJMMJGDO-TVLGPKEFSA-N 0.000 claims description 3
- OOFATALNAVRPAV-FAODQTPUSA-N [(5R)-2-amino-5-deuterio-5-(3-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC(=CC=C1)OC)N)([2H])[2H] OOFATALNAVRPAV-FAODQTPUSA-N 0.000 claims description 3
- OVBKNDHONMIVNP-FAODQTPUSA-N [(5R)-2-amino-5-deuterio-5-(3-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C=1C=C(C=CC=1)C)N)([2H])[2H] OVBKNDHONMIVNP-FAODQTPUSA-N 0.000 claims description 3
- SLYSOBIJVWDZBX-TVLGPKEFSA-N [(5R)-2-amino-5-deuterio-5-(4-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)F)N)([2H])[2H] SLYSOBIJVWDZBX-TVLGPKEFSA-N 0.000 claims description 3
- NNHGKCQLDVXYIJ-FAODQTPUSA-N [(5R)-2-amino-5-deuterio-5-(4-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)OC)N)([2H])[2H] NNHGKCQLDVXYIJ-FAODQTPUSA-N 0.000 claims description 3
- UYMFMALBUNANPK-FAODQTPUSA-N [(5R)-2-amino-5-deuterio-5-(4-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C)N)([2H])[2H] UYMFMALBUNANPK-FAODQTPUSA-N 0.000 claims description 3
- PUQUKIZPSCRUKV-MSMSUOMYSA-N [(5R)-2-amino-5-deuterio-5-[4-(dideuteriocarbamoyl)phenyl]-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(N([2H])[2H])=O)N)([2H])[2H] PUQUKIZPSCRUKV-MSMSUOMYSA-N 0.000 claims description 3
- AVNGYQDTSGNWIT-UQSZZEIXSA-N [(5R)-5-(4-acetylphenyl)-2-amino-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(C)=O)N)([2H])[2H] AVNGYQDTSGNWIT-UQSZZEIXSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-SXBXRDHOSA-N [(5R)-5-deuterio-2-(dideuterioamino)-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-SXBXRDHOSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-MSMSUOMYSA-N [(5R)-5-deuterio-2-(dideuterioamino)-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-MSMSUOMYSA-N 0.000 claims description 3
- ZUEYSOISQIRWHI-BUYVNXHGSA-N [(5S)-2-amino-5-(1,3-benzodioxol-5-yl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC2=C(OCO2)C=C1)N)([2H])[2H] ZUEYSOISQIRWHI-BUYVNXHGSA-N 0.000 claims description 3
- VNMMWJDNBNERJS-BCYJYSMKSA-N [(5S)-2-amino-5-(2-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1)Br)N)([2H])[2H] VNMMWJDNBNERJS-BCYJYSMKSA-N 0.000 claims description 3
- VVJQQPNTDSBJGO-SWMWQOICSA-N [(5S)-2-amino-5-(2-chloro-3-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=CC=C1)F)Cl)N)([2H])[2H] VVJQQPNTDSBJGO-SWMWQOICSA-N 0.000 claims description 3
- LBPGBBOUMNREPT-SWMWQOICSA-N [(5S)-2-amino-5-(2-chloro-4-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=C(C=C1)F)Cl)N)([2H])[2H] LBPGBBOUMNREPT-SWMWQOICSA-N 0.000 claims description 3
- KFIICSGBLRSJPA-SWMWQOICSA-N [(5S)-2-amino-5-(2-chloro-5-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC(=C1)F)Cl)N)([2H])[2H] KFIICSGBLRSJPA-SWMWQOICSA-N 0.000 claims description 3
- MDJJAEKJZSERFA-SWMWQOICSA-N [(5S)-2-amino-5-(2-chloro-6-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1F)Cl)N)([2H])[2H] MDJJAEKJZSERFA-SWMWQOICSA-N 0.000 claims description 3
- FOGWFWDJRVMWKA-BCYJYSMKSA-N [(5S)-2-amino-5-(2-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1)Cl)N)([2H])[2H] FOGWFWDJRVMWKA-BCYJYSMKSA-N 0.000 claims description 3
- MHLYYVLTOYRHRL-BCYJYSMKSA-N [(5S)-2-amino-5-(3-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC=C1)Br)N)([2H])[2H] MHLYYVLTOYRHRL-BCYJYSMKSA-N 0.000 claims description 3
- VLJVMMHJHOBTIG-SWMWQOICSA-N [(5S)-2-amino-5-(3-chloro-4-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=C(C=C1)F)Cl)N)([2H])[2H] VLJVMMHJHOBTIG-SWMWQOICSA-N 0.000 claims description 3
- RSTVETSPNBACFW-SWMWQOICSA-N [(5S)-2-amino-5-(3-chloro-5-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC(=C1)F)Cl)N)([2H])[2H] RSTVETSPNBACFW-SWMWQOICSA-N 0.000 claims description 3
- SDGJJRNVCOGVAG-BCYJYSMKSA-N [(5S)-2-amino-5-(3-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC=C1)Cl)N)([2H])[2H] SDGJJRNVCOGVAG-BCYJYSMKSA-N 0.000 claims description 3
- OZSTYEYYIZOGJR-JBJBDCEVSA-N [(5S)-2-amino-5-(3-cyanophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC=C1)C#N)N)([2H])[2H] OZSTYEYYIZOGJR-JBJBDCEVSA-N 0.000 claims description 3
- OTWZNPQDTYKBKE-BCYJYSMKSA-N [(5S)-2-amino-5-(4-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Br)N)([2H])[2H] OTWZNPQDTYKBKE-BCYJYSMKSA-N 0.000 claims description 3
- PUQUKIZPSCRUKV-BCYJYSMKSA-N [(5S)-2-amino-5-(4-carbamoylphenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C(N)=O)N)([2H])[2H] PUQUKIZPSCRUKV-BCYJYSMKSA-N 0.000 claims description 3
- CSOJGNWXIRSATJ-SWMWQOICSA-N [(5S)-2-amino-5-(4-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=C(C=C1)Cl)F)N)([2H])[2H] CSOJGNWXIRSATJ-SWMWQOICSA-N 0.000 claims description 3
- UHJBGKUXTPVWDM-SWMWQOICSA-N [(5S)-2-amino-5-(4-chloro-3-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=C(C=C1)Cl)F)N)([2H])[2H] UHJBGKUXTPVWDM-SWMWQOICSA-N 0.000 claims description 3
- AIMVCVQVRLGLRH-QSMXCNCDSA-N [(5S)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuterio-2-methylpropane-1-sulfonate Chemical compound CC(C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H])C AIMVCVQVRLGLRH-QSMXCNCDSA-N 0.000 claims description 3
- XXJFDCICKAWHSZ-FMIPQBBESA-N [(5S)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuteriobutane-1-sulfonate Chemical compound C(CCC)(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] XXJFDCICKAWHSZ-FMIPQBBESA-N 0.000 claims description 3
- VCNOSHCOKRGAFH-XSMZCWJBSA-N [(5S)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuterioethanesulfonate Chemical compound C(C)(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] VCNOSHCOKRGAFH-XSMZCWJBSA-N 0.000 claims description 3
- SYCCMZVSTUCIHF-OGQRJONUSA-N [(5S)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 2-deuteriopropane-2-sulfonate Chemical compound CC(C)(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)[2H] SYCCMZVSTUCIHF-OGQRJONUSA-N 0.000 claims description 3
- WRYVLBKLGDJEPA-WTDRUJNCSA-N [(5S)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] benzenesulfonate Chemical compound C1(=CC=CC=C1)S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Cl)N WRYVLBKLGDJEPA-WTDRUJNCSA-N 0.000 claims description 3
- AFTCLAGEFNWDOX-VONWFZARSA-N [(5S)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] trideuteriomethanesulfonate Chemical compound C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])([2H])[2H] AFTCLAGEFNWDOX-VONWFZARSA-N 0.000 claims description 3
- ULTBFGINDWYOAO-JBJBDCEVSA-N [(5S)-2-amino-5-(4-cyanophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C#N)N)([2H])[2H] ULTBFGINDWYOAO-JBJBDCEVSA-N 0.000 claims description 3
- FXUAIYVNGBMTBB-SWMWQOICSA-N [(5S)-2-amino-5-(5-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC(=C1)Cl)F)N)([2H])[2H] FXUAIYVNGBMTBB-SWMWQOICSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-ACJDSKBTSA-N [(5S)-2-amino-5-deuterio-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N)([2H])[2H] JSENTRJIUXBCNY-ACJDSKBTSA-N 0.000 claims description 3
- PLRFYKHCOKBGPL-BCYJYSMKSA-N [(5S)-2-amino-5-deuterio-4-oxo-5-[3-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC=C1)C(F)(F)F)N)([2H])[2H] PLRFYKHCOKBGPL-BCYJYSMKSA-N 0.000 claims description 3
- AAMMUKIEONIWFZ-NSPYSDJFSA-N [(5S)-2-amino-5-deuterio-4-oxo-5-[6-(trifluoromethyl)pyridin-3-yl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C=1C=NC(=CC=1)C(F)(F)F)N)([2H])[2H] AAMMUKIEONIWFZ-NSPYSDJFSA-N 0.000 claims description 3
- RBMNZNDOGRAYCO-LPXFZLGISA-N [(5S)-2-amino-5-deuterio-4-oxo-5-phenylfuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=CC=C1)N)([2H])[2H] RBMNZNDOGRAYCO-LPXFZLGISA-N 0.000 claims description 3
- RKSVAVTXWOUTKP-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(2,3-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=CC=C1)Cl)Cl)N)([2H])[2H] RKSVAVTXWOUTKP-SWMWQOICSA-N 0.000 claims description 3
- UEIXZUNCVZXURR-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(2,3-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=CC=C1)F)F)N)([2H])[2H] UEIXZUNCVZXURR-SWMWQOICSA-N 0.000 claims description 3
- UZMVSVRIMLYTFC-MOHNLXNOSA-N [(5S)-2-amino-5-deuterio-5-(2,3-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=CC=C1)OC)OC)N)([2H])[2H] UZMVSVRIMLYTFC-MOHNLXNOSA-N 0.000 claims description 3
- FSAGXOYHOPYBLM-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(2,4-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=C(C=C1)Cl)Cl)N)([2H])[2H] FSAGXOYHOPYBLM-SWMWQOICSA-N 0.000 claims description 3
- MRANPYZDQRPVMQ-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(2,4-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=C(C=C1)F)F)N)([2H])[2H] MRANPYZDQRPVMQ-SWMWQOICSA-N 0.000 claims description 3
- UTLRIETUSATVLU-MOHNLXNOSA-N [(5S)-2-amino-5-deuterio-5-(2,4-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=C(C=C1)OC)OC)N)([2H])[2H] UTLRIETUSATVLU-MOHNLXNOSA-N 0.000 claims description 3
- NRSDXXYHJSXZIM-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(2,5-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC(=C1)Cl)Cl)N)([2H])[2H] NRSDXXYHJSXZIM-SWMWQOICSA-N 0.000 claims description 3
- ZINZHCFHUQQGOC-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(2,5-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC(=C1)F)F)N)([2H])[2H] ZINZHCFHUQQGOC-SWMWQOICSA-N 0.000 claims description 3
- ABEXEQNVKLVRTN-MOHNLXNOSA-N [(5S)-2-amino-5-deuterio-5-(2,5-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC(=C1)OC)OC)N)([2H])[2H] ABEXEQNVKLVRTN-MOHNLXNOSA-N 0.000 claims description 3
- UXLGTLOXBAKPJN-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(2,6-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1F)F)N)([2H])[2H] UXLGTLOXBAKPJN-SWMWQOICSA-N 0.000 claims description 3
- NWAYGVMPOGETRW-MOHNLXNOSA-N [(5S)-2-amino-5-deuterio-5-(2,6-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1OC)OC)N)([2H])[2H] NWAYGVMPOGETRW-MOHNLXNOSA-N 0.000 claims description 3
- RMXWGKXYBJIXBE-BCYJYSMKSA-N [(5S)-2-amino-5-deuterio-5-(2-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1)F)N)([2H])[2H] RMXWGKXYBJIXBE-BCYJYSMKSA-N 0.000 claims description 3
- YXFYSGOXEMVSMD-JBJBDCEVSA-N [(5S)-2-amino-5-deuterio-5-(2-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1)OC)N)([2H])[2H] YXFYSGOXEMVSMD-JBJBDCEVSA-N 0.000 claims description 3
- QRSZCGYMHKMZOG-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(3,4-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=C(C=C1)F)F)N)([2H])[2H] QRSZCGYMHKMZOG-SWMWQOICSA-N 0.000 claims description 3
- ORZDSIAWTHZDNR-MOHNLXNOSA-N [(5S)-2-amino-5-deuterio-5-(3,4-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=C(C=C1)OC)OC)N)([2H])[2H] ORZDSIAWTHZDNR-MOHNLXNOSA-N 0.000 claims description 3
- TYLBFGJWPMBOSE-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(3,5-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC(=C1)Cl)Cl)N)([2H])[2H] TYLBFGJWPMBOSE-SWMWQOICSA-N 0.000 claims description 3
- GCYOEKPCUFCJOL-SWMWQOICSA-N [(5S)-2-amino-5-deuterio-5-(3,5-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC(=C1)F)F)N)([2H])[2H] GCYOEKPCUFCJOL-SWMWQOICSA-N 0.000 claims description 3
- NNENVKFNMNCPJU-MOHNLXNOSA-N [(5S)-2-amino-5-deuterio-5-(3,5-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC(=C1)OC)OC)N)([2H])[2H] NNENVKFNMNCPJU-MOHNLXNOSA-N 0.000 claims description 3
- NHVBIMUJMMJGDO-BCYJYSMKSA-N [(5S)-2-amino-5-deuterio-5-(3-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC=C1)F)N)([2H])[2H] NHVBIMUJMMJGDO-BCYJYSMKSA-N 0.000 claims description 3
- OOFATALNAVRPAV-JBJBDCEVSA-N [(5S)-2-amino-5-deuterio-5-(3-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC(=CC=C1)OC)N)([2H])[2H] OOFATALNAVRPAV-JBJBDCEVSA-N 0.000 claims description 3
- OVBKNDHONMIVNP-JBJBDCEVSA-N [(5S)-2-amino-5-deuterio-5-(3-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C=1C=C(C=CC=1)C)N)([2H])[2H] OVBKNDHONMIVNP-JBJBDCEVSA-N 0.000 claims description 3
- SLYSOBIJVWDZBX-BCYJYSMKSA-N [(5S)-2-amino-5-deuterio-5-(4-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound [2H]C([2H])(C1=CC=CC=C1)S(=O)(=O)OC1=C(N)O[C@]([2H])(C1=O)C1=CC=C(F)C=C1 SLYSOBIJVWDZBX-BCYJYSMKSA-N 0.000 claims description 3
- NNHGKCQLDVXYIJ-JBJBDCEVSA-N [(5S)-2-amino-5-deuterio-5-(4-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)OC)N)([2H])[2H] NNHGKCQLDVXYIJ-JBJBDCEVSA-N 0.000 claims description 3
- UYMFMALBUNANPK-JBJBDCEVSA-N [(5S)-2-amino-5-deuterio-5-(4-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C)N)([2H])[2H] UYMFMALBUNANPK-JBJBDCEVSA-N 0.000 claims description 3
- PUQUKIZPSCRUKV-GLKBSBJWSA-N [(5S)-2-amino-5-deuterio-5-[4-(dideuteriocarbamoyl)phenyl]-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C(N([2H])[2H])=O)N)([2H])[2H] PUQUKIZPSCRUKV-GLKBSBJWSA-N 0.000 claims description 3
- AVNGYQDTSGNWIT-MOHNLXNOSA-N [(5S)-5-(4-acetylphenyl)-2-amino-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C(C)=O)N)([2H])[2H] AVNGYQDTSGNWIT-MOHNLXNOSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-QBUMZBQMSA-N [(5S)-5-deuterio-2-(dideuterioamino)-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-QBUMZBQMSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-GLKBSBJWSA-N [(5S)-5-deuterio-2-(dideuterioamino)-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-GLKBSBJWSA-N 0.000 claims description 3
- VNMMWJDNBNERJS-PZHCDCHGSA-N [2-amino-5-(2-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1)Br)N)([2H])[2H] VNMMWJDNBNERJS-PZHCDCHGSA-N 0.000 claims description 3
- VVJQQPNTDSBJGO-SMNVOWQRSA-N [2-amino-5-(2-chloro-3-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=CC=C1)F)Cl)N)([2H])[2H] VVJQQPNTDSBJGO-SMNVOWQRSA-N 0.000 claims description 3
- LBPGBBOUMNREPT-SMNVOWQRSA-N [2-amino-5-(2-chloro-4-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=C(C=C1)F)Cl)N)([2H])[2H] LBPGBBOUMNREPT-SMNVOWQRSA-N 0.000 claims description 3
- KFIICSGBLRSJPA-SMNVOWQRSA-N [2-amino-5-(2-chloro-5-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC(=C1)F)Cl)N)([2H])[2H] KFIICSGBLRSJPA-SMNVOWQRSA-N 0.000 claims description 3
- MDJJAEKJZSERFA-SMNVOWQRSA-N [2-amino-5-(2-chloro-6-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1F)Cl)N)([2H])[2H] MDJJAEKJZSERFA-SMNVOWQRSA-N 0.000 claims description 3
- FOGWFWDJRVMWKA-PZHCDCHGSA-N [2-amino-5-(2-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1)Cl)N)([2H])[2H] FOGWFWDJRVMWKA-PZHCDCHGSA-N 0.000 claims description 3
- MHLYYVLTOYRHRL-PZHCDCHGSA-N [2-amino-5-(3-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC=C1)Br)N)([2H])[2H] MHLYYVLTOYRHRL-PZHCDCHGSA-N 0.000 claims description 3
- VLJVMMHJHOBTIG-SMNVOWQRSA-N [2-amino-5-(3-chloro-4-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=C(C=C1)F)Cl)N)([2H])[2H] VLJVMMHJHOBTIG-SMNVOWQRSA-N 0.000 claims description 3
- RSTVETSPNBACFW-SMNVOWQRSA-N [2-amino-5-(3-chloro-5-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC(=C1)F)Cl)N)([2H])[2H] RSTVETSPNBACFW-SMNVOWQRSA-N 0.000 claims description 3
- PUQUKIZPSCRUKV-PZHCDCHGSA-N [2-amino-5-(4-carbamoylphenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(N)=O)N)([2H])[2H] PUQUKIZPSCRUKV-PZHCDCHGSA-N 0.000 claims description 3
- CSOJGNWXIRSATJ-SMNVOWQRSA-N [2-amino-5-(4-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=C(C=C1)Cl)F)N)([2H])[2H] CSOJGNWXIRSATJ-SMNVOWQRSA-N 0.000 claims description 3
- AIMVCVQVRLGLRH-VTPVYVOOSA-N [2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuterio-2-methylpropane-1-sulfonate Chemical compound CC(C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H])C AIMVCVQVRLGLRH-VTPVYVOOSA-N 0.000 claims description 3
- VCNOSHCOKRGAFH-KAFRBFAESA-N [2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuterioethanesulfonate Chemical compound C(C)(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] VCNOSHCOKRGAFH-KAFRBFAESA-N 0.000 claims description 3
- OWVBFOSPAPHJPY-XGWWUZNLSA-N [2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuteriopropane-1-sulfonate Chemical compound C(CC)(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] OWVBFOSPAPHJPY-XGWWUZNLSA-N 0.000 claims description 3
- SYCCMZVSTUCIHF-CJVWNTGVSA-N [2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 2-deuteriopropane-2-sulfonate Chemical compound CC(C)(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Cl)N)[2H] SYCCMZVSTUCIHF-CJVWNTGVSA-N 0.000 claims description 3
- WRYVLBKLGDJEPA-FCFVPJCTSA-N [2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] benzenesulfonate Chemical compound C1(=CC=CC=C1)S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Cl)N WRYVLBKLGDJEPA-FCFVPJCTSA-N 0.000 claims description 3
- AFTCLAGEFNWDOX-JLZJBEKYSA-N [2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] trideuteriomethanesulfonate Chemical compound C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])([2H])[2H] AFTCLAGEFNWDOX-JLZJBEKYSA-N 0.000 claims description 3
- ULTBFGINDWYOAO-CXVUVLKYSA-N [2-amino-5-(4-cyanophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C#N)N)([2H])[2H] ULTBFGINDWYOAO-CXVUVLKYSA-N 0.000 claims description 3
- FXUAIYVNGBMTBB-SMNVOWQRSA-N [2-amino-5-(5-chloro-2-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC(=C1)Cl)F)N)([2H])[2H] FXUAIYVNGBMTBB-SMNVOWQRSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-IVYHWKMISA-N [2-amino-5-deuterio-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N)([2H])[2H] JSENTRJIUXBCNY-IVYHWKMISA-N 0.000 claims description 3
- CGQRROWINGCADB-PZHCDCHGSA-N [2-amino-5-deuterio-4-oxo-5-[2-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1)C(F)(F)F)N)([2H])[2H] CGQRROWINGCADB-PZHCDCHGSA-N 0.000 claims description 3
- PLRFYKHCOKBGPL-PZHCDCHGSA-N [2-amino-5-deuterio-4-oxo-5-[3-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC=C1)C(F)(F)F)N)([2H])[2H] PLRFYKHCOKBGPL-PZHCDCHGSA-N 0.000 claims description 3
- VFISNKLCDZPVJT-SMNVOWQRSA-N [2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] (4-chlorophenyl)-dideuteriomethanesulfonate Chemical compound ClC1=CC=C(C=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] VFISNKLCDZPVJT-SMNVOWQRSA-N 0.000 claims description 3
- USWANUYZCZPJOE-SMNVOWQRSA-N [2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-[4-(trifluoromethyl)phenyl]methanesulfonate Chemical compound FC(C1=CC=C(C=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H])(F)F USWANUYZCZPJOE-SMNVOWQRSA-N 0.000 claims description 3
- AAMMUKIEONIWFZ-BAVZAHHNSA-N [2-amino-5-deuterio-4-oxo-5-[6-(trifluoromethyl)pyridin-3-yl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C=1C=NC(=CC=1)C(F)(F)F)N)([2H])[2H] AAMMUKIEONIWFZ-BAVZAHHNSA-N 0.000 claims description 3
- YSMZUVFIILJEIO-SMNVOWQRSA-N [2-amino-5-deuterio-5-(2,2-difluoro-1,3-benzodioxol-5-yl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC2=C(OC(O2)(F)F)C=C1)N)([2H])[2H] YSMZUVFIILJEIO-SMNVOWQRSA-N 0.000 claims description 3
- RKSVAVTXWOUTKP-SMNVOWQRSA-N [2-amino-5-deuterio-5-(2,3-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=CC=C1)Cl)Cl)N)([2H])[2H] RKSVAVTXWOUTKP-SMNVOWQRSA-N 0.000 claims description 3
- UEIXZUNCVZXURR-SMNVOWQRSA-N [2-amino-5-deuterio-5-(2,3-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=CC=C1)F)F)N)([2H])[2H] UEIXZUNCVZXURR-SMNVOWQRSA-N 0.000 claims description 3
- UZMVSVRIMLYTFC-FEBFSFJESA-N [2-amino-5-deuterio-5-(2,3-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=CC=C1)OC)OC)N)([2H])[2H] UZMVSVRIMLYTFC-FEBFSFJESA-N 0.000 claims description 3
- FSAGXOYHOPYBLM-SMNVOWQRSA-N [2-amino-5-deuterio-5-(2,4-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=C(C=C1)Cl)Cl)N)([2H])[2H] FSAGXOYHOPYBLM-SMNVOWQRSA-N 0.000 claims description 3
- MRANPYZDQRPVMQ-SMNVOWQRSA-N [2-amino-5-deuterio-5-(2,4-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=C(C=C1)F)F)N)([2H])[2H] MRANPYZDQRPVMQ-SMNVOWQRSA-N 0.000 claims description 3
- UTLRIETUSATVLU-FEBFSFJESA-N [2-amino-5-deuterio-5-(2,4-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=C(C=C1)OC)OC)N)([2H])[2H] UTLRIETUSATVLU-FEBFSFJESA-N 0.000 claims description 3
- NRSDXXYHJSXZIM-SMNVOWQRSA-N [2-amino-5-deuterio-5-(2,5-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC(=C1)Cl)Cl)N)([2H])[2H] NRSDXXYHJSXZIM-SMNVOWQRSA-N 0.000 claims description 3
- ABEXEQNVKLVRTN-FEBFSFJESA-N [2-amino-5-deuterio-5-(2,5-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC(=C1)OC)OC)N)([2H])[2H] ABEXEQNVKLVRTN-FEBFSFJESA-N 0.000 claims description 3
- UXLGTLOXBAKPJN-SMNVOWQRSA-N [2-amino-5-deuterio-5-(2,6-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1F)F)N)([2H])[2H] UXLGTLOXBAKPJN-SMNVOWQRSA-N 0.000 claims description 3
- YXFYSGOXEMVSMD-CXVUVLKYSA-N [2-amino-5-deuterio-5-(2-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1)OC)N)([2H])[2H] YXFYSGOXEMVSMD-CXVUVLKYSA-N 0.000 claims description 3
- OEYDNENGPIRMQX-CXVUVLKYSA-N [2-amino-5-deuterio-5-(2-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1)C)N)([2H])[2H] OEYDNENGPIRMQX-CXVUVLKYSA-N 0.000 claims description 3
- QRSZCGYMHKMZOG-SMNVOWQRSA-N [2-amino-5-deuterio-5-(3,4-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=C(C=C1)F)F)N)([2H])[2H] QRSZCGYMHKMZOG-SMNVOWQRSA-N 0.000 claims description 3
- ORZDSIAWTHZDNR-FEBFSFJESA-N [2-amino-5-deuterio-5-(3,4-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=C(C=C1)OC)OC)N)([2H])[2H] ORZDSIAWTHZDNR-FEBFSFJESA-N 0.000 claims description 3
- GCYOEKPCUFCJOL-SMNVOWQRSA-N [2-amino-5-deuterio-5-(3,5-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC(=C1)F)F)N)([2H])[2H] GCYOEKPCUFCJOL-SMNVOWQRSA-N 0.000 claims description 3
- NNENVKFNMNCPJU-FEBFSFJESA-N [2-amino-5-deuterio-5-(3,5-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC(=C1)OC)OC)N)([2H])[2H] NNENVKFNMNCPJU-FEBFSFJESA-N 0.000 claims description 3
- NHVBIMUJMMJGDO-PZHCDCHGSA-N [2-amino-5-deuterio-5-(3-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC=C1)F)N)([2H])[2H] NHVBIMUJMMJGDO-PZHCDCHGSA-N 0.000 claims description 3
- OVBKNDHONMIVNP-CXVUVLKYSA-N [2-amino-5-deuterio-5-(3-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C=1C=C(C=CC=1)C)N)([2H])[2H] OVBKNDHONMIVNP-CXVUVLKYSA-N 0.000 claims description 3
- SLYSOBIJVWDZBX-PZHCDCHGSA-N [2-amino-5-deuterio-5-(4-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)F)N)([2H])[2H] SLYSOBIJVWDZBX-PZHCDCHGSA-N 0.000 claims description 3
- NNHGKCQLDVXYIJ-CXVUVLKYSA-N [2-amino-5-deuterio-5-(4-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)OC)N)([2H])[2H] NNHGKCQLDVXYIJ-CXVUVLKYSA-N 0.000 claims description 3
- UYMFMALBUNANPK-CXVUVLKYSA-N [2-amino-5-deuterio-5-(4-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C)N)([2H])[2H] UYMFMALBUNANPK-CXVUVLKYSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-MFUGHSMMSA-N [5-deuterio-2-(dideuterioamino)-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-MFUGHSMMSA-N 0.000 claims description 3
- JSENTRJIUXBCNY-OHBKQDJBSA-N [5-deuterio-2-(dideuterioamino)-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-OHBKQDJBSA-N 0.000 claims description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
- MMFVUSUBVIGUTJ-MCABGJGTSA-N ethyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)OCC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 MMFVUSUBVIGUTJ-MCABGJGTSA-N 0.000 claims description 3
- MMFVUSUBVIGUTJ-IBHOJZALSA-N ethyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)OCC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] MMFVUSUBVIGUTJ-IBHOJZALSA-N 0.000 claims description 3
- AFLVHFCDVZDJMV-UQSZZEIXSA-N ethyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio-(4-fluorophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)OCC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F AFLVHFCDVZDJMV-UQSZZEIXSA-N 0.000 claims description 3
- MMFVUSUBVIGUTJ-MNUYRWSUSA-N ethyl 4-[(2S)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)OCC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 MMFVUSUBVIGUTJ-MNUYRWSUSA-N 0.000 claims description 3
- AFLVHFCDVZDJMV-MOHNLXNOSA-N ethyl 4-[(2S)-5-amino-2-deuterio-4-[dideuterio-(4-fluorophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)OCC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F AFLVHFCDVZDJMV-MOHNLXNOSA-N 0.000 claims description 3
- MMFVUSUBVIGUTJ-PABLSKFYSA-N ethyl 4-[5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)OCC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 MMFVUSUBVIGUTJ-PABLSKFYSA-N 0.000 claims description 3
- MMFVUSUBVIGUTJ-AJNUTEPASA-N ethyl 4-[5-amino-2-deuterio-4-[dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)OCC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] MMFVUSUBVIGUTJ-AJNUTEPASA-N 0.000 claims description 3
- AFLVHFCDVZDJMV-FEBFSFJESA-N ethyl 4-[5-amino-2-deuterio-4-[dideuterio-(4-fluorophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)OCC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F AFLVHFCDVZDJMV-FEBFSFJESA-N 0.000 claims description 3
- 208000002672 hepatitis B Diseases 0.000 claims description 3
- PSAULDWOMOUESB-SDDABLCMSA-N methyl 2-[4-[(2R)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]phenyl]-2,2-dideuterioacetate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C=C1)C(C(=O)OC)([2H])[2H])=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 PSAULDWOMOUESB-SDDABLCMSA-N 0.000 claims description 3
- PSAULDWOMOUESB-RCOSHLFASA-N methyl 2-[4-[5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]phenyl]-2,2-dideuterioacetate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C=C1)C(C(=O)OC)([2H])[2H])=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1 PSAULDWOMOUESB-RCOSHLFASA-N 0.000 claims description 3
- RGIFNCKGVFMIBW-FSDVPALTSA-N methyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]-2-fluorobenzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC(=C(C(=O)OC)C=C1)F)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] RGIFNCKGVFMIBW-FSDVPALTSA-N 0.000 claims description 3
- LHPXMEBVGVXZCU-UQKYZCROSA-N methyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)OC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] LHPXMEBVGVXZCU-UQKYZCROSA-N 0.000 claims description 3
- JSDTVFPAMURSIJ-QEZZGCPKSA-N methyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio-(4-fluorophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]-2-fluorobenzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC(=C(C(=O)OC)C=C1)F)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F JSDTVFPAMURSIJ-QEZZGCPKSA-N 0.000 claims description 3
- AXSCPUIPPULDSJ-QDQVUVIPSA-N methyl 4-[(2R)-5-amino-2-deuterio-4-[dideuterio-(4-fluorophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)OC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F AXSCPUIPPULDSJ-QDQVUVIPSA-N 0.000 claims description 3
- RGIFNCKGVFMIBW-ZNNREADOSA-N methyl 4-[5-amino-2-deuterio-4-[dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]-2-fluorobenzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC(=C(C(=O)OC)C=C1)F)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] RGIFNCKGVFMIBW-ZNNREADOSA-N 0.000 claims description 3
- LHPXMEBVGVXZCU-ZISFLIOPSA-N methyl 4-[5-amino-2-deuterio-4-[dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)OC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] LHPXMEBVGVXZCU-ZISFLIOPSA-N 0.000 claims description 3
- AXSCPUIPPULDSJ-PYQSMLQDSA-N methyl 4-[5-amino-2-deuterio-4-[dideuterio-(4-fluorophenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)OC)C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=C(C=C1)F AXSCPUIPPULDSJ-PYQSMLQDSA-N 0.000 claims description 3
- DPHARIGBAQCBOI-IHUBAHEHSA-M potassium 4-[(2R)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)[O-])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1.[K+] DPHARIGBAQCBOI-IHUBAHEHSA-M 0.000 claims description 3
- DPHARIGBAQCBOI-MLQIDUTGSA-M potassium 4-[(2S)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)[O-])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1.[K+] DPHARIGBAQCBOI-MLQIDUTGSA-M 0.000 claims description 3
- DPHARIGBAQCBOI-GWQFHZSFSA-M potassium 4-[5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)[O-])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1.[K+] DPHARIGBAQCBOI-GWQFHZSFSA-M 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- QYIDGOSNHRXSGM-IHUBAHEHSA-M sodium 4-[(2R)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)[O-])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1.[Na+] QYIDGOSNHRXSGM-IHUBAHEHSA-M 0.000 claims description 3
- QYIDGOSNHRXSGM-MLQIDUTGSA-M sodium 4-[(2S)-5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)[O-])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1.[Na+] QYIDGOSNHRXSGM-MLQIDUTGSA-M 0.000 claims description 3
- QYIDGOSNHRXSGM-GWQFHZSFSA-M sodium 4-[5-amino-2-deuterio-4-[dideuterio(phenyl)methyl]sulfonyloxy-3-oxofuran-2-yl]benzoate Chemical compound NC1=C(C(C(O1)([2H])C1=CC=C(C(=O)[O-])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=CC=CC=C1.[Na+] QYIDGOSNHRXSGM-GWQFHZSFSA-M 0.000 claims description 3
- RWLRAWDGKPVDEC-SMNVOWQRSA-N FC1=CC=C(C=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] Chemical compound FC1=CC=C(C=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] RWLRAWDGKPVDEC-SMNVOWQRSA-N 0.000 claims description 2
- RWLRAWDGKPVDEC-SWMWQOICSA-N FC1=CC=C(C=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] Chemical compound FC1=CC=C(C=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] RWLRAWDGKPVDEC-SWMWQOICSA-N 0.000 claims description 2
- RWLRAWDGKPVDEC-LMOOGUKRSA-N FC1=CC=C(C=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] Chemical compound FC1=CC=C(C=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] RWLRAWDGKPVDEC-LMOOGUKRSA-N 0.000 claims description 2
- 208000005176 Hepatitis C Diseases 0.000 claims description 2
- KCTOHJCNLJXFHH-DOQSXBGYSA-N NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] Chemical compound NC1=C(C([C@@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] KCTOHJCNLJXFHH-DOQSXBGYSA-N 0.000 claims description 2
- KCTOHJCNLJXFHH-RXDFUYOHSA-N NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] Chemical compound NC1=C(C([C@](O1)([2H])C1=CC=C(C(=O)O[2H])C=C1)=O)OS(=O)(=O)C([2H])([2H])C1=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H] KCTOHJCNLJXFHH-RXDFUYOHSA-N 0.000 claims description 2
- 206010047249 Venous thrombosis Diseases 0.000 claims description 2
- JSENTRJIUXBCNY-LCGWKYONSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N)([2H])[2H] JSENTRJIUXBCNY-LCGWKYONSA-N 0.000 claims description 2
- VFISNKLCDZPVJT-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] (4-chlorophenyl)-dideuteriomethanesulfonate Chemical compound ClC1=CC=C(C=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] VFISNKLCDZPVJT-LMOOGUKRSA-N 0.000 claims description 2
- JSENTRJIUXBCNY-WAIRCIRWSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] JSENTRJIUXBCNY-WAIRCIRWSA-N 0.000 claims description 2
- USWANUYZCZPJOE-LMOOGUKRSA-N [(5R)-2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-[4-(trifluoromethyl)phenyl]methanesulfonate Chemical compound FC(C1=CC=C(C=C1)C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H])(F)F USWANUYZCZPJOE-LMOOGUKRSA-N 0.000 claims description 2
- JSENTRJIUXBCNY-QEKVJDPJSA-N [(5R)-5-deuterio-2-(dideuterioamino)-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-QEKVJDPJSA-N 0.000 claims description 2
- JSENTRJIUXBCNY-WJIRBHGISA-N [(5R)-5-deuterio-2-(dideuterioamino)-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(O[C@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-WJIRBHGISA-N 0.000 claims description 2
- OWVBFOSPAPHJPY-GNWBAJMMSA-N [(5S)-2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuteriopropane-1-sulfonate Chemical compound C(CC)(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] OWVBFOSPAPHJPY-GNWBAJMMSA-N 0.000 claims description 2
- JSENTRJIUXBCNY-QNXICOSOSA-N [(5S)-2-amino-5-deuterio-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N)([2H])[2H] JSENTRJIUXBCNY-QNXICOSOSA-N 0.000 claims description 2
- CGQRROWINGCADB-BCYJYSMKSA-N [(5S)-2-amino-5-deuterio-4-oxo-5-[2-(trifluoromethyl)phenyl]furan-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1)C(F)(F)F)N)([2H])[2H] CGQRROWINGCADB-BCYJYSMKSA-N 0.000 claims description 2
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- OEYDNENGPIRMQX-JBJBDCEVSA-N [(5S)-2-amino-5-deuterio-5-(2-methylphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C=CC=C1)C)N)([2H])[2H] OEYDNENGPIRMQX-JBJBDCEVSA-N 0.000 claims description 2
- JSENTRJIUXBCNY-XUSSZIMOSA-N [(5S)-5-deuterio-2-(dideuterioamino)-4-oxo-5-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=C(C(=C(C(=C1[2H])[2H])C(F)(F)F)[2H])[2H])N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-XUSSZIMOSA-N 0.000 claims description 2
- JSENTRJIUXBCNY-STYNUSDBSA-N [(5S)-5-deuterio-2-(dideuterioamino)-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(O[C@@](C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-STYNUSDBSA-N 0.000 claims description 2
- ZUEYSOISQIRWHI-QZMCOADOSA-N [2-amino-5-(1,3-benzodioxol-5-yl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC2=C(OCO2)C=C1)N)([2H])[2H] ZUEYSOISQIRWHI-QZMCOADOSA-N 0.000 claims description 2
- SDGJJRNVCOGVAG-PZHCDCHGSA-N [2-amino-5-(3-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC=C1)Cl)N)([2H])[2H] SDGJJRNVCOGVAG-PZHCDCHGSA-N 0.000 claims description 2
- OZSTYEYYIZOGJR-CXVUVLKYSA-N [2-amino-5-(3-cyanophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC=C1)C#N)N)([2H])[2H] OZSTYEYYIZOGJR-CXVUVLKYSA-N 0.000 claims description 2
- OTWZNPQDTYKBKE-PZHCDCHGSA-N [2-amino-5-(4-bromophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Br)N)([2H])[2H] OTWZNPQDTYKBKE-PZHCDCHGSA-N 0.000 claims description 2
- UHJBGKUXTPVWDM-SMNVOWQRSA-N [2-amino-5-(4-chloro-3-fluorophenyl)-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=C(C=C1)Cl)F)N)([2H])[2H] UHJBGKUXTPVWDM-SMNVOWQRSA-N 0.000 claims description 2
- XXJFDCICKAWHSZ-STOMFCJLSA-N [2-amino-5-(4-chlorophenyl)-5-deuterio-4-oxofuran-3-yl] 1,1-dideuteriobutane-1-sulfonate Chemical compound C(CCC)(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)Cl)N)([2H])[2H] XXJFDCICKAWHSZ-STOMFCJLSA-N 0.000 claims description 2
- JSENTRJIUXBCNY-YFRIWGRKSA-N [2-amino-5-deuterio-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N)([2H])[2H] JSENTRJIUXBCNY-YFRIWGRKSA-N 0.000 claims description 2
- ZINZHCFHUQQGOC-SMNVOWQRSA-N [2-amino-5-deuterio-5-(2,5-difluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC(=C1)F)F)N)([2H])[2H] ZINZHCFHUQQGOC-SMNVOWQRSA-N 0.000 claims description 2
- NWAYGVMPOGETRW-FEBFSFJESA-N [2-amino-5-deuterio-5-(2,6-dimethoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1OC)OC)N)([2H])[2H] NWAYGVMPOGETRW-FEBFSFJESA-N 0.000 claims description 2
- RMXWGKXYBJIXBE-PZHCDCHGSA-N [2-amino-5-deuterio-5-(2-fluorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=C(C=CC=C1)F)N)([2H])[2H] RMXWGKXYBJIXBE-PZHCDCHGSA-N 0.000 claims description 2
- TYLBFGJWPMBOSE-SMNVOWQRSA-N [2-amino-5-deuterio-5-(3,5-dichlorophenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC(=C1)Cl)Cl)N)([2H])[2H] TYLBFGJWPMBOSE-SMNVOWQRSA-N 0.000 claims description 2
- OOFATALNAVRPAV-CXVUVLKYSA-N [2-amino-5-deuterio-5-(3-methoxyphenyl)-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC(=CC=C1)OC)N)([2H])[2H] OOFATALNAVRPAV-CXVUVLKYSA-N 0.000 claims description 2
- AVNGYQDTSGNWIT-FEBFSFJESA-N [5-(4-acetylphenyl)-2-amino-5-deuterio-4-oxofuran-3-yl] dideuterio(phenyl)methanesulfonate Chemical compound C1(=CC=CC=C1)C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(C)=O)N)([2H])[2H] AVNGYQDTSGNWIT-FEBFSFJESA-N 0.000 claims description 2
- JSENTRJIUXBCNY-GSSLVRRLSA-N [5-deuterio-2-(dideuterioamino)-4-oxo-5-[4-(trifluoromethyl)phenyl]furan-3-yl] dideuterio-(2,3,4,5,6-pentadeuteriophenyl)methanesulfonate Chemical compound C1(=C(C(=C(C(=C1[2H])[2H])[2H])[2H])[2H])C(S(=O)(=O)OC1=C(OC(C1=O)([2H])C1=CC=C(C=C1)C(F)(F)F)N([2H])[2H])([2H])[2H] JSENTRJIUXBCNY-GSSLVRRLSA-N 0.000 claims description 2
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Images
Classifications
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- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/66—Nitrogen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Definitions
- Isotopically-stabilized tetronimide compounds comprising one or more deuterium atoms, derivatives, and intermediates, thereof, including methods for their synthesis, pharmaceutical compositions thereof, and methods of using these compounds to interact with target molecules in cell-free samples, cell- and tissue-based assays, animal models, and in a subject are disclosed.
- One aspect relates to molecules that modulate the expression or catalytic activity of aspartyl (asparaginyl) p-hydroxylase (ASPH) within or on the surface of a cell.
- Other aspects of the invention relate to use of the molecules disclosed herein to diagnose, ameliorate, or treat cell proliferation disorders and related diseases.
- Related aspects include uses of the compounds to modulate the activity of viruses, as anti-hyperlipidemia agents, and as agents to ameliorate or treat thrombosis and related cardiovascular and metabolic disorders.
- Aspartyl(asparaginyl)- ⁇ -hydroxylase is an iron-dependent dioxygenase that catalyzes the hydroxylation of ⁇ carbons of aspartic acid and asparagine residues in calcium binding Epidermal Growth Factor (cbEGF)-like domains of a variety of proteins, including Notch and Notch ligand homologs (Dinchuk, Focht et al. 2002) extracellular matrix proteins, and low density lipoprotein (LDL) receptors.
- cbEGF Epidermal Growth Factor
- ASPH was first observed to be involved in the hydroxylation of a specific aspartic acid residue in the blood coagulation cascade proteins (Drakenberg, Fernlund et al.
- ASPH is generally classified as a peptide-aspartate beta-dioxygenase (EC 1.14.11.16), a member of the alpha-ketoglutarate-dependent hydroxylases superfamily, which catalyzes the following chemical reaction, facilitated by iron as a cofactor.
- peptide-L-aspartate+2-oxoglutarate+O 2 peptide-3-hydroxy-L-aspartate+succinate+CO 2 (Reaction 1)
- ASPH is not normally expressed in adult cells (Lavaissiere, Jia et al. 1996), but is expressed during invasion of the uterine wall by trophoblasts during development of the placenta (Gundogan, Elwood et al. 2007).
- ASPH is overexpressed in a variety of tumors, including hepatocellular, cholangiocarcinoma, gastric cancer, pancreatic cancer, non-small cell lung cancer, glioblastoma multiform, osteosarcoma, cervical cancer, ovarian cancer and breast cancer (Yang, Song et al. 2010), and enhances signaling in the Notch pathway (Cantarini, de la Monte et al. 2006).
- FIG. 1 sets forth an illustration showing the Activation of Notch Signaling Pathway by ASPH.
- FIG. 2 Panels A-H, plus domain key
- FIG. 3 Panels A-G, plus domain key both set forth illustrations showing the Locations of Epitopes of Interest on ASPH.
- ASPH substrates are illustrated in FIG. 4 and FIG. 5 .
- Prediction of ASPH substrates is based upon the protein possessing A) a cbEGF domain and B) the consensus sequence CX[ D / N ]X 4 [Y/F]XC (SEQ ID NO: 1).
- Notch signaling proteins not only including the receptors Notch1-4, but many of the known ligands such as Jagged1&2 and Dll1&4, but also known Notch pathway modulator human homologues of Crumbs from Drosophila .
- ASPH is known to hydroxylate lipid receptor proteins, including Lrp1.
- ASPH substrate Gas6 is the ligand of the Tyro3, Axel and Mer (TAM) kinases, which have been implicated in cancer (Wu, Ma et al. 2018).
- TAM Axel and Mer
- Known ASPH substrates including the fibrillins are involved in the release of TGF-beta, which is implicated in cancer (Furler, Nixon et al. 2018).
- ASPH hydroxylated substrates are found in nearly all of the blood coagulation proteins involved in thrombosis (see panel D in FIG.
- ASPH expression is expected to have a cascade of effects, but may have particular value in the treatment of cancer, as well as thrombosis and lipid/cholesterol associated cardiovascular diseases.
- ASPH expression may be correlated with viral infection, particularly with hepatitis B, D and human papillomavirus, and may enhance viral replication either directly, by enhancing cellular proliferation, or by activating proteins (such as URG11/VWCE) that are specifically upregulated by the virus.
- ASPH is known to contain multiple phosphorylation sites (Tong, Gao et al. 2013), including T748. Phosphorylation of ASPH is known to alter the expression and function of ASPH (Borgas, Gao et al. 2015), and plays a potential role in migration and tissue invasion of hepatocellular carcinoma (Borgas, Gao et al. 2015). Antibodies selective for ASPH phosphorylation state should be useful in the diagnosis of cancer and distinguishing ASPH expressed in normal cells compared to ASPH expressed in tumor cells.
- U.S. Pat. No. 9,771,356 discloses ASPH modulating compounds that possess a stereocenter that is easily racemized, which cannot be isolated as pure enantiomers under experimental conditions. While deuterated versions of existing drug products are known (Timmins, G. S., 2014), the use of deuterium to limit racemization of the tetronimide ring core, permitting stable isolation of pure enantiomers as disclosed herein, is surprising and unexpected. The deuterated versions of many tetronimide compounds disclosed herein have superior chemical and drug product properties, compared to the properties of undeuterated tetronimide compounds, precursor compounds, intermediates, and related derivatives.
- Isotopically-stabilized tetronimide compounds comprising one or more deuterium atoms, derivatives, and intermediates, thereof, including methods for their synthesis, pharmaceutical compositions thereof, and methods of using these compounds to interact with target molecules in cell-free samples, cell- and tissue-based assays, animal models, and in human and animal subjects are disclosed.
- One aspect of the invention is directed to a deuterated compound of any one of formulas ⁇ I-A, I-B, I-C, I-D, I-E, I-F, I-G, or I-H ⁇ :
- Ar 1 is a substituted or unsubstituted C 6 -C 20 aryl or 5- to 20-membered heteroaryl;
- V 1 , V 2 , V 3 , V 4 , V 5 , or Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , Z 7 , Z 8 , or Z 9 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance;
- W is C(O), C(S), or S(O) 2 ;
- Y is a single bond, O, CR 50 R 51 , or NR 52 when W is CO and W is a single bond, CR 50 R 51 or NR 52 when X is SO 2 , and
- R 53 is selected from the group consisting of substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted C 6 -C 20 aryl, substituted or unsubstituted C 7 -C 26 arylalkyl, substituted or unsubstituted 5 to 20-membered heteroaryl, and substituted or unsubstituted 6-26 membered heteroarylalkyl; and
- Ar 2 designated as an unsubstituted or substituted C 6 -C 20 heteroaryl is selected from the group consisting of: phenyl; naphthyl; pyridyl; pyridone; pyrimidine; pyradazine; pyrazine; purine; furan; thiophene; oxazole; thiazole; isoxazole; isothiazole; oxadiazole; thiadiazole; pyrrole; imidazole; triazole; tetrazole; and diazepine.
- deuterated compound of any one of formulas ⁇ I-A, I-B, I-C, I-D, I-E, I-F, I-G, or I-H ⁇ to facilitate the diagnosis, treatment, or ameliorating of a condition associated with cell proliferation disorders and related diseases.
- Related aspects include uses of the deuterated compounds to modulate the activity of viruses, or as anti-hyperlipidemia agents, and as agents to ameliorate or treat thrombosis and related cardiovascular and metabolic disorders.
- FIG. 1 sets forth an illustration showing the Activation of Notch Signaling Pathway by ASPH.
- FIG. 2 (Panels A-H, plus a polypeptide domain key) sets forth an illustration showing experimentally confirmed and computationally predicted substrates of ASPH, including those found in the following types of proteins: A. Notch signaling pathway, B. Lipid receptors, C. Blood coagulation cascade proteins, D. Thrombospondins, E. Complement cascade proteins, F. FAT cadherin domain proteins, G. Bone associated proteins, and H. 7-transmembrane domain containing proteins.
- FIG. 3 sets forth an illustration showing experimentally confirmed and computationally predicted substrates of ASPH (continued), including those found in the following types of proteins: A. TGF-b containing proteins, B. Platelet associated proteins, C. Eye/retina associated proteins, D. Mammary cancer metastasis proteins, E. Slit proteins, F. Miscellaneous proteins, and G. Drosophila homologues.
- FIG. 4 sets forth an illustration demonstrating the mechanism of action of tetronimide modulating compounds.
- Deuterium can stabilize a stereo-center, or can be used to slow down or suppress metabolism.
- Compound #2066 has a deuterium at the stereocenter, as well as two deuteriums at the benzylic position adjacent to the “C” ring.
- Compound #2084 has two deuteriums on the amino of the tetronimide ring.
- Compound #2085 has a deuterium at the stereocenter, two deuteriums at the benzylic position adjacent to the “C” ring, and two deuteriums on the amino of the tetronimide ring.
- Compound #1072 has two deuteriums at the benzylic position adjacent to the “C” ring, and the “C” ring is perdeuterated.
- Compound #2087 is deuterated at the stereocenter, the benzylic position adjacent to the “C” ring, two deuteriums on the amine of the tetronimide, and the “C” ring is perdeuterated.
- Compound #1084 has the “A” ring perdeuterated.
- FIG. 5 illustrates the synthesis of non-deuterated ASPH tetronimide modulator compounds in Scheme 1.
- Scheme 2 illustrates the synthesis of compounds of the formulas ⁇ I-A ⁇ and ⁇ I-B ⁇ .
- Scheme 3 illustrates the synthesis of compounds of the formula ⁇ I-D ⁇ .
- Scheme 4 illustrates the synthesis of compounds of the formula ⁇ I-E ⁇ .
- FIG. 6 illustrates an alternate synthesis of compounds of the formula ⁇ I-D ⁇ .
- Scheme 6 illustrates the synthesis of perdeuterated phenylmethanesulfonyl chloride.
- Scheme 7 illustrates the synthesis of compounds of the formula ⁇ I-F ⁇ .
- FIG. 7 illustrates the synthesis of compounds of the formula ⁇ I-G ⁇ according to Scheme 8.
- Scheme 9 illustrates the synthesis of compounds of the formula ⁇ I-G ⁇ .
- Scheme 10 illustrates the synthesis of compounds of the formula ⁇ I-H ⁇ .
- FIG. 8 illustrates the Activities of Undeuterated, Racemic, and Deuterated Enantiomers of Tetronimide Modulator Compounds against ASPH in Liver Microsome Assays.
- FIG. 9 illustrates the Activities of Specific Compounds against MCF-7 Cells In Vitro.
- FIGS. 10 - 1 to 10 - 62 illustrate the raw and tabulated NMR spectra of 21 compounds over 62 pages for the compounds listed in Table 3, entitled “Table of Compounds by Informal Number and Chemical Name with NMR Spectra”.
- cell refers to one or more cells which can be in an isolated or cultured state, as in a cell line comprising a homogeneous or heterogeneous population of cells, or in a tissue sample, or as part of an organism, such as a transgenic animal.
- modulator refers to one or more activities, such as stimulation of activity, inhibition of enzymatic activity, stimulation of protein expression, or suppression of protein expression.
- stimulation of activity include allosteric activators.
- inhibition of enzymatic activity include allosteric deactivators, competitive inhibitors, non-competitive inhibitors, and uncompetitive inhibitors.
- stimulation of protein expression include kinase inhibitors or activators.
- suppression of protein expression include kinase inhibitors or activators.
- amino acid encompasses both naturally occurring and non-naturally occurring amino acids unless otherwise designated.
- isotopic enrichment factor means the ratio between the isotopic abundance and the natural abundance of a specified isotope.
- isotopologue means a species in which the chemical structure differs from a specific compound of the invention only in the isotopic composition thereof.
- cell refers to one or more cells which can be in an isolated or cultured state, as in a cell line comprising a homogeneous or heterogeneous population of cells, or in a tissue sample, or as part of an organism, such as an unmodified or a transgenic animal.
- an effective amount means an amount of the substance in question which produces a statistically significant effect.
- an “effective amount” for therapeutic uses is the amount of the composition comprising an active compound herein required to provide a clinically significant alteration in a measurable trait. Such effective amounts will be determined using routine optimization techniques and are dependent on the particular condition to be treated, the condition of the patient, the route of administration, dosage required for the compounds of the invention is manifested as that which induces a statistically significant difference between treatment and control groups.
- a “therapeutically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result.
- a therapeutically effective amount of modulator may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the modulator to elicit a desired response in the individual. Dosage regimens may be adjusted to provide the optimum therapeutic response.
- a therapeutically-effective amount is also one in which any toxic or detrimental effects of the modulator are outweighed by the therapeutically beneficial effects.
- a “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result.
- a prophylactically effective amount can be determined as described above for the therapeutically-effective amount. Typically, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically-effective amount.
- cell proliferative disorder refers to conditions in which unregulated or abnormal growth, or both, of cells can lead to the development of an unwanted condition or disease, which may or may not be cancerous.
- Exemplary cell proliferative disorders that may be treated with the compounds of the invention encompass a variety of conditions wherein cell division is deregulated.
- Exemplary cell proliferative disorder include, but are not limited to, neoplasms, benign tumors, malignant tumors, pre-cancerous conditions, in situ tumors, encapsulated tumors, metastatic tumors, liquid tumors, solid tumors, immunological tumors, hematological tumors, cancers, carcinomas, leukemias, lymphomas, sarcomas, and rapidly dividing cells.
- a cell proliferative disorder includes a precancer or a precancerous condition.
- a cell proliferative disorder includes cancer.
- the methods and uses provided herein can be or may be used to treat or alleviate a symptom of cancer or to identify suitable candidates for such purposes.
- cancer includes solid tumors, as well as, hematologic tumors and/or malignancies.
- precancer cell or precancerous cell is a cell manifesting a cell proliferative disorder that is a precancer or a precancerous condition.
- cancer cell or “cancerous cell” is a cell manifesting a cell proliferative disorder that is a cancer. Any reproducible means of measurement may be used to identify cancer cells or precancerous cells. Cancer cells or precancerous cells can be identified by histological typing or grading of a tissue sample (e.g., a biopsy sample). Cancer cells or precancerous cells can be identified through the use of appropriate molecular markers.
- treating describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of a compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder.
- the term “treat” can also include treatment of a cell in vitro or an animal model.
- a compound of the present invention can or may also be used to prevent a relevant disease, condition or disorder, or used to identify suitable candidates for such purposes.
- preventing,” “prevent,” or “protecting against” describes reducing or eliminating the onset of the symptoms or complications of such disease, condition or disorder.
- the term “alleviate” is meant to describe a process by which the severity of a sign or symptom of a disorder is decreased.
- a sign or symptom can be alleviated without being eliminated.
- the administration of pharmaceutical compositions of the invention can or may lead to the elimination of a sign or symptom, however, elimination is not required.
- Effective dosages should be expected to decrease the severity of a sign or symptom.
- a sign or symptom of a disorder such as cancer, which can occur in multiple locations, is alleviated if the severity of the cancer is decreased within at least one of multiple locations.
- a “subject” is interchangeable with a “subject in need thereof”, both of which refer to a subject having a cell proliferation disorder, or a subject having an increased risk of developing such disorder relative to the population at large.
- a “subject” includes a mammal.
- the mammal can be e.g., a human or appropriate non-human mammal, such as primate, mouse, rat, dog, cat, cow, horse, goat, camel, sheep or a pig.
- the subject can also be a bird or fowl.
- the mammal is a human.
- a subject in need thereof can be one who has been previously diagnosed or identified as having cancer or a precancerous condition.
- a subject in need thereof can also be one who has (e.g., is suffering from) cancer or a precancerous condition.
- a subject in need thereof can be one who has an increased risk of developing such disorder relative to the population at large (i.e., a subject who is predisposed to developing such disorder relative to the population at large).
- a subject in need thereof can have a precancerous condition.
- the term “animal” includes human beings.
- optionally substituted moiety refers to either unsubstituted chemical moiety (e.g., alkyl, aryl, heteroaryl, etc.) or a chemical moiety having designated substituents replacing one or more hydrogen atoms on one or more carbons of the hydrocarbon backbone.
- substituents can include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sul
- substituted aryl or heteroaryl refers to aromatic or heteroaromatic rings may contain one or more substituents such as —OH, SH, —CN, —F, —C, —Br, —R, —NO 2 —NO, —NH 2 , —NHR, —NRR, —C(O)R, —C(O)OH, —C(O)OR, —C(O)NH 2 , —C(O)NHR, —C(O)NRR, and the like where each R is independently (C 1 -C 5 ) alkyl, substituted (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, substituted (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, substituted (C 2 -C 6 ) alkynyl, (C 5 -C 20 ) aryl, substituted (C 5 -C 5 )
- arylalkyl or an “aralkyl” moiety is an alkyl substituted with an aryl (e.g., phenylmethyl (benzyl)).
- alkylaryl moiety is an aryl substituted with an alkyl (e.g., methylphenyl).
- a “derivative” of a compound X refers to a form of X in which one or more reactive groups on the compound have been derivatized with a substituent group.
- Peptide derivatives include pep tides in which an amino acid side chain, the peptide backbone, or the amino' or carboxy-terminus has been derivatized (e.g., peptidic compounds with 5 methylated amide linkages).
- an “analogue” of a compound X refers to a compound which retains chemical structures of X necessary for functional activity of X yet which also contains certain chemical structures which differ from X.
- An analogue of a naturally-occurring peptide is a peptide which includes one or more non-naturally-occurring amino acids.
- mimetic refers to a compound having similar functional and/or structural properties to another known compound or a particular fragment of that known compound.
- a “mimetic” of a compound X refers to a compound in which chemical structures of X necessary for functional activity of X have been replaced with other chemical structures which mimic the conformation of X.
- mimetic, and in particular, peptidomimetic is intended to include isosteres.
- cyclic group is intended to include cyclic saturated or unsaturated (i.e., aromatic) group having from about 3 to 10, preferably about 4 to 8, and more preferably about 5 to 7, carbon atoms.
- exemplary cyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cyclooctyl. Cyclic groups may be unsubstituted or substituted at one or more ring positions.
- a cyclic group may be substituted with halogens, alkyls, cycloalkyls, alkenyls, alkynyls, aryls, heterocycles, hydroxyls, aminos, nitros, thiols, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, sulfonates, selenoethers, ketones, aldehydes, esters, CF 3 , CN, or the like.
- heterocyclic group is intended to include cyclic saturated or unsaturated (i.e., aromatic) group having from about 3 to 10, preferably about 4 to 8, and more preferably about 5 to 7, carbon atoms, wherein the ring structure includes about one to four heteroatoms.
- Heterocyclic groups include pyrrolidine, oxolane, thiolane, imidazole, oxazole, piperidine, piperazine, morpholine and pyridine.
- the heterocyclic ring can be substituted at one or more positions with such substituents as, for example, halogens, alkyls, cycloalkyls, alkenyls, alkynyls, aryls, other heterocycles, hydroxyl, amino, nitro thiol, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, CF 3 , CN, or the like.
- Heterocycles may also be bridged or fused to other cyclic groups as described below.
- Aryl includes groups with aromaticity, including “conjugated,” or multicyclic systems with at least one aromatic ring and do not contain any heteroatom in the ring structure. Examples include phenyl, benzyl, 1,2,3,4-tetrahydronaphthalenyl, etc.
- Heteroaryl groups are aryl groups, as defined above, except having from one to four heteroatoms in the ring structure, and may also be referred to as “aryl heterocycles” or “heteroaromatics.”
- the term “heteroaryl” is intended to include a stable 5-, 6-, or 7-membered monocyclic or 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic aromatic heterocyclic ring which consists of carbon atoms and one or more heteroatoms, e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6 heteroatoms, or e.g., 1, 2, 3, 4, 5, or 6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen and sulfur.
- the nitrogen atom may be substituted or unsubstituted (i.e., N or NR wherein R is H or other substituents, as defined).
- heteroaryl groups include pyrrole, furan, thiophene, thiazole, isothiazole, imidazole, triazole, tetrazole, pyrazole, oxazole, isoxazole, pyridine, pyrazine, pyridazine, pyrimidine, and the like.
- aryl and heteroaryl include multicyclic aryl and heteroaryl groups, e.g., tricyclic, bicyclic, e.g., naphthalene, benzoxazole, benzodioxazole, benzothiazole, benzoimidazole, benzothiophene, methylenedioxyphenyl, quinoline, isoquinoline, naphthrydine, indole, benzofuran, purine, benzofuran, deazapurine, indolizine.
- the rings In the case of multicyclic aromatic rings, only one of the rings needs to be aromatic (e.g., 2,3-dihydroindole), although all of the rings may be aromatic (e.g., quinoline).
- the second ring can also be fused or bridged.
- the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring can be substituted at one or more ring positions (e.g., the ring-forming carbon or heteroatom such as N) with such substituents as described above, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphonato, phosphinato, amino (including alkylamino, dialkylamino, ary
- polycyclic group as used herein is intended to refer to two or more saturated or unsaturated (i.e., aromatic) cyclic rings in which two or more carbons are common to two adjoining rings, e.g., the rings are “fused rings”. Rings that are joined through non-adjacent atoms are termed “bridged” rings.
- Each of the rings of the polycyclic group can be substituted with such substituents as described above, as for example, halogens, alkyls, cycloalkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, CF 3 , CN, or the like.
- substituents as described above, as for example, halogens, alkyls, cycloalkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyl
- modifying group and “modifying group” are used interchangeably to describe a chemical group directly or indirectly attached, generally, to a peptidic structure.
- a modifying group(s) can be directly attached by covalent coupling to a peptidic structure or a modifying group(s) can be attached indirectly by a stable non-covalent association.
- the compounds described herein include the compounds themselves, as well as their salts, their solvates, and their prodrugs, if applicable.
- a salt for example, can be formed between an anion and a positively charged group (e.g., amino) on a substituted benzene compound.
- Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, and acetate (e.g., trifluoroacetate).
- pharmaceutically acceptable anion refers to an anion suitable for forming a pharmaceutically acceptable salt.
- a salt can also be formed between a cation and a negatively charged group (e.g., carboxylate) on a substituted benzene compound.
- Suitable cations include sodium ion, potassium ion, magnesium ion, calcium ion, and an ammonium cation such as tetramethylammonium ion.
- the substituted benzene compounds also include those salts containing quaternary nitrogen atoms.
- prodrugs include esters and other pharmaceutically acceptable derivatives, which, upon administration to a subject, are capable of providing active substituted benzene compounds.
- the compounds of the present invention can also exist in either hydrated or unhydrated (the anhydrous) form or as solvates with other solvent molecules.
- Nonlimiting examples of hydrates include monohydrates, dihydrates, etc.
- Nonlimiting examples of solvates include ethanol solvates, acetone solvates, etc.
- Solvate means solvent addition forms that contain either stoichiometric or non-stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate. If the solvent is water the solvate formed is a hydrate; and if the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of one or more molecules of water with one molecule of the substance in which the water retains its molecular state as H 2 O.
- the structural formula of the compound generally represents a certain isomer for convenience in some cases, but the present invention includes all isomers, such as geometrical isomers, optical isomers based on an asymmetrical carbon, stereoisomers, tautomers, and the like, it being understood that not all isomers may have the same level of activity.
- a crystal polymorphism may be present for the compounds represented by the formula. It is noted that any crystal form, crystal form mixture, or anhydride or hydrate thereof is included in the scope of the present invention. Furthermore, so-called metabolite which is produced by degradation of the present compound in vivo is included in the scope of the present invention.
- Tautomer is one of two or more structural isomers that exist in equilibrium and is readily converted from one isomeric form to another. This conversion results in the formal migration of a hydrogen atom accompanied by a switch of adjacent conjugated double bonds. Tautomers exist as a mixture of a tautomeric set in solution. In solutions where tautomerization is possible, a chemical equilibrium of the tautomers will be reached. The exact ratio of the tautomers depends on several factors, including temperature, solvent and pH. The concept of tautomers that are interconvertable by tautomerizations is called tautomerism.
- keto-enol tautomerism a simultaneous shift of electrons and a hydrogen atom occurs.
- Ring-chain tautomerism arises as a result of the aldehyde group (—CHO) in a sugar chain molecule reacting with one of the hydroxy groups (—OH) in the same molecule to give it a cyclic (ring-shaped) form as exhibited by glucose.
- tautomeric pairs are: ketone-enol, amide-nitrile, lactam-lactim, amide-imidic acid tautomerism in heterocyclic rings (e.g., in nucleobases such as guanine, thymine and cytosine), imine-enamine and enamine-enamine.
- ketone-enol tautomerism in the tetronimide ring system is illustrated below.
- a small molecule is a compound that is less than 2000 Daltons in mass.
- the molecular mass of the small molecule is preferably less than 1000 Daltons, more preferably less than 600 Daltons, e.g., the compound is less than 500 Daltons, 400 Daltons, 300 Daltons, 200 Daltons, or 100 Daltons.
- transitional term “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps.
- the transitional phrase “consisting of” excludes any element, step, or ingredient not specified in the claim.
- the transitional phrase “consisting essentially of” limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention.
- Purified compounds are at least 60% by weight (dry weight) the compound of interest.
- the preparation is at least 75%, more preferably at least 90%, and most preferably at least 99%, by weight the compound of interest.
- a purified compound is one that is at least 90%, 91%, 92%, 93%, 94%, 95%, 98%, 99%, or 100% (w/w) of the desired compound by weight. Purity is measured by any appropriate standard method, for example, by column chromatography, thin layer chromatography, or high-performance liquid chromatography (HPLC) analysis.
- a purified or isolated polynucleotide (ribonucleic acid (RNA) or deoxyribonucleic acid (DNA)) is free of the genes or sequences that flank it in its naturally-occurring state.
- One aspect of the invention is directed to a deuterated compound of any one of formulas ⁇ I-A, I-B, I-C, I-D, I-E, I-F, I-G, or I-H ⁇ :
- Ar 1 is a substituted or unsubstituted C 6 -C 20 aryl or 5- to 20-membered heteroaryl;
- V 1 , V 2 , V 3 , V 4 , V 5 , or Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , Z 7 , Z 8 , or Z 9 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance;
- W is C(O), C(S), or S(O) 2 ;
- Y is a single bond, O, CR 50 R 51 , or NR 52 when W is CO and W is a single bond, CR 50 R 51 or NR 52 when X is SO 2 , and
- R 53 is selected from the group consisting of substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted C 6 -C 20 aryl, substituted or unsubstituted C 7 -C 26 arylalkyl, substituted or unsubstituted 5 to 20-membered heteroaryl, and substituted or unsubstituted 6-26 membered heteroarylalkyl; and
- Ar 2 designated as an unsubstituted or substituted C 6 -C 20 heteroaryl is selected from the group consisting of: phenyl; naphthyl; pyridyl; pyridone; pyrimidine; pyradazine; pyrazine; purine; furan; thiophene; oxazole; thiazole; isoxazole; isothiazole; oxadiazole; thiadiazole; pyrrole; imidazole; triazole; tetrazole; and diazepine.
- Another aspect is directed to a deuterated compound having formula ⁇ I-A ⁇ ,
- V 1 is deuterium (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
- Another aspect is directed to a deuterated compound having formula ⁇ I-B ⁇ ,
- V 1 , V 2 , and V 3 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance;
- Another aspect is directed to a deuterated compound having formula ⁇ I-C ⁇ ,
- V 1 , V 2 , V 3 , or Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
- Another aspect is directed to a deuterated compound having formula ⁇ I-D ⁇ ,
- V 4 or V 5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
- Another aspect is directed to a deuterated compound having formula ⁇ I-E ⁇ ,
- V 1 , V 2 , V 3 , V 4 , or V 5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
- Another aspect is directed to a deuterated compound having formula ⁇ I-F ⁇ ,
- V 2 , V 3 , or Z 1 , Z 2 , Z 3 , Z 4 , or Z 5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
- Another aspect is directed to a deuterated compound having formula ⁇ I-G ⁇ ,
- V 1 , V 2 , V 3 , V 4 , V 5 , or Z 1 , Z 2 , Z 3 , Z 4 , Z 5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
- Another aspect is directed to a deuterated compound having formula ⁇ I-H ⁇ ,
- V 2 , V 3 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , Z 7 , Z 8 , or Z 9 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
- Another aspect relates to a deuterated compound having any one of formulas ⁇ I-A, I-B, I-C, I-D, I-E, I-F, or I-G ⁇
- Ar 1 is a substituted C 6 -C 20 aryl group selected from the group consisting of one or more substituents selected from the group consisting of mono F, Cl, or Br at any position; difluoro or dichloro at different positions; mono and di methyl any position; mono di and trifluoromethyl; mono and di OMe at any position; mono and di chlorophenyl at any position; CO 2 Me; F and CO 2 Me; CO 2 Et; C(O)CH3; C(O)NH 2 ; C(O):ND 2 ; COO ⁇ Na + ; COO ⁇ K + ; [COO ⁇ ] 2 Mg +2 ; [COO ⁇ ] 2 Ca +2 ; mono and di CN at different positions; phenyl; CF 3 ; CO 3 Me; CO
- R 53 is Ar 2 , designated as an unsubstituted or substituted C 6 -C 20 heteroaryl selected from the group consisting of: phenyl; naphthyl; pyridyl; pyridone; pyrimidine; pyradazine; pyrazine; purine; furan; thiophene; oxazole; thiazole; isoxazole; isothiazole; oxadiazole; thiadiazole; pyrrole; imidazole; triazole; tetrazole; and diazepine.
- Ar 2 designated as an unsubstituted or substituted C 6 -C 20 heteroaryl selected from the group consisting of: phenyl; naphthyl; pyridyl; pyridone; pyrimidine; pyradazine; pyrazine; purine; furan; thiophene; oxazole; thiazole; iso
- R 53 is an unsubstituted or substituted phenyl, selected from the group consisting of one or more substituents selected from the group consisting of: mono F, C, or Br at any position; difluoro or dichloro at different positions; mono and di methyl any position; mono di and trifluoromethyl; mono and di OMe at any position; mono and di chlorophenyl at any position; CO 2 Me; F and CO 2 Me; CO 2 Et; C(O)CH 3 ; C(O)NH 2 ; C(O):ND 2 ; COO ⁇ Na + ; COO ⁇ K + ; [COO ⁇ ] 2 Mg +2 ; [COO ⁇ ] 2 Ca +2 ; mono and di CN at different positions; phenyl; CF 3 ; CO 3 Me; CO 2 D; CF 3 ; CO 2 Me; benzo[d][1,3]dixol-5
- Another aspect relates to a deuterated compound wherein any atom not designated as deuterium is present at its natural isotopic abundance, and where the percentage of isotopic enrichment for each designated deuterium is at least 50%.
- Related aspects also include compounds where the enrichment for each designated deuterium is at least 75%, 90%, 95%, and 99%.
- Another aspect of the invention relates to a method of preparing a deuterated compound having any of formulas ⁇ I-A, I-B, I-C, I-F ⁇ by contacting an undeuterated precursor compound with a suitable base and a deuterated solvent.
- said suitable base is selected from the group consisting of LiOD, NaOD, KOD, CsOD, Ba(OD) 2 , Ca(OD) 2 , Mg(OD) 2 , Mn(OD) 2 , Li 2 CO 3 , Na 2 CO 3 , K 2 CO 3 , Cs 2 CO 3 , MgCO 3 , and CaCO 3 .
- said deuterated solvent is D 2 O.
- Another aspect relates to a method of preparing a deuterated compound having formula ⁇ I-D ⁇ , by contacting an undeuterated precursor compound with deuterium in an acidic medium.
- said deuterium in an acidic medium is selected from the group consisting of one or more of D 2 O, DF, DCl, DBr, DI, D 2 NO 3 , D 2 SO 4 , CF 3 SO 3 D, CD 3 CO 2 D, CF 3 CO 2 D, CCl 3 CO 2 D.
- Another aspect relates to a method of preparing a deuterated compound having any one of formulas ⁇ I-E, I-G ⁇ , by contacting an undeuterated precursor compound with an acidic medium followed by a deuterated basic medium.
- said acidic medium is selected from the group consisting of one or more of D 2 O, DF, DCl, DBr, DI, D 2 NO 3 , D 2 SO 4 , CF 3 SO 3 D, CD 3 CO 2 D, CF 3 CO 2 D, CCl 3 CO 2 D.
- said deuterated basic medium is selected from the group consisting of LiOD, NaOD, KO D, Ba(OD) 2 , Ca(OD) 2 , Mg(OD) 2 , Mn(OD) 2 , Li 2 CO 3 , Na 2 CO 3 , K 2 CO 3 , Cs 2 CO 3 , MgCO 3 , and CaCO 3 .
- Another aspect relates to a method of preparing a deuterated compound of Claim 1 having any one of formulas ⁇ I-F, I-H ⁇ , by contacting an undeuterated precursor tetronimide compound with a deuterated sulfonyl chloride.
- said deuterated sulfonyl chloride is selected from the group consisting of d5-sulfonyl chloride and d7-sulfonyl chloride.
- Another specific aspect is a deuterated compound of having formula I-B.
- Another specific aspect is a deuterated compound of having formula I-B, wherein Ar 2 is phenyl, and Ar 1 is a substituted C 6 -C 20 aryl group selected from the group consisting of one or more substituents selected from the group consisting of mono F, C, or Br at any position; difluoro or dichloro at different positions; mono and di methyl any position; mono di and trifluoromethyl; mono and di OMe at any position; mono and di chlorophenyl at any position; CO 2 Me; F and CO 2 Me; CO 2 Et; C(O)CH 3 ; C(O)NH 2 ; C(O):ND 2 ; COO ⁇ Na + ; COO ⁇ K + ; [COO ⁇ ] 2 Mg +2 ; [COO ⁇ ] 2 Ca +2 ; mono and di CN at different positions; phenyl; CF 3 ; CO 3 Me; CO 2 D; CF 3 ; CO 2 Me; benzo[d][1,3]
- compositions comprising a deuterated compound of Formulas ⁇ I-A ⁇ through ⁇ I-H ⁇ , noted above, or a pharmaceutical acceptable salt thereof and a pharmaceutically-acceptable carrier.
- compositions comprising a deuterated compound of Formulas ⁇ I-A ⁇ through ⁇ I-H ⁇ , noted above or a pharmaceutical acceptable ester, metabolite, prodrug, or solvate thereof and a pharmaceutically-acceptable carrier.
- compositions comprising a deuterated compound selected from the group consisting of a racemic, (R), and (S) named form of a compound, noted above or a pharmaceutical acceptable salt thereof and a pharmaceutically-acceptable carrier.
- compositions comprising a deuterated compound selected from the group consisting of a racemic, (R), and (S) named form of a compound, noted above or a pharmaceutical acceptable ester, metabolite, prodrug, or solvate thereof and a pharmaceutically-acceptable carrier.
- aspects of the invention relate to a method of treating or ameliorating one or more conditions associated with a proliferative cellular disorder by administering one or more doses of a pharmaceutical composition comprising one or more deuterated compounds in one or more amounts effective to treat or ameliorate one or more conditions associated with the proliferative cellular disorder.
- proliferative cellular disorder is selected from the group consisting of cancer, pancreatic cancer, lung cancer, breast cancer, glioblastomal cancer, neruobalstoma, osteosarcoma, ovarian cancer, cervical cancer, head and neck cancer, cholangiocarcinoma, and hepatocellular carcinoma.
- Other related aspects of the invention relate to a method of treating or ameliorating one or more conditions associated with hyperlipidemia, blood coagulation, complement activation and viral infections by administering one or more doses of a pharmaceutical composition comprising one or more deuterated compounds in one or more amounts effective to treat or ameliorate one or more conditions associated with the proliferative cellular disorder.
- One aspect of the invention relates to a method of treating hypercholesterolemia, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound selected from the group consisting of one or more deuterated compounds in one or more amounts effective to treat or ameliorate one or more conditions associated with hyperlipidemia.
- One aspect of the invention relates to a method of treating a viral disease, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound selected from the group consisting of one or more deuterated compounds in one or more amounts effective to treat or ameliorate one or more conditions associated with viral disease.
- One aspect also relates to a method wherein said viral disease is selected from the group consisting of hepatitis B, hepatitis C, hepatitis D, and human papillomavirus.
- One aspect of the invention relates to a method of treating blood coagulation disorders, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound selected from the group consisting of one or more deuterated compounds in one or more amounts effective to treat or ameliorate one or more conditions associated with blood coagulation.
- One aspect also relates to a method wherein said blood coagulation disorder is selected from the group consisting of thrombosis, venous thrombosis, myocardial thrombosis, cerebral thrombosis, pulmonary thrombosis, and hepatic thrombosis.
- compositions including pharmaceutical compositions, comprising the compounds of the invention, noted above.
- One aspect of the invention is directed to a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a therapeutically effective amount of the compound or salt disclosed above.
- Still another aspect of the invention relates to a method for pharmaceutical formulation of previously described compounds for use in oral and intravenous applications, and in implantable materials.
- Another aspect of the present invention relates to a pharmaceutical composition including a pharmaceutically acceptable carrier and a compound according to the aspects of the present invention.
- the pharmaceutical composition can contain one or more of the above-identified compounds of the present invention.
- the pharmaceutical composition of the present invention will include a compound of the present invention or its pharmaceutically acceptable salt, as well as a pharmaceutically acceptable carrier.
- pharmaceutically acceptable carrier refers to any suitable adjuvants, carriers, excipients, or stabilizers, and can be in solid or liquid form such as, tablets, capsules, powders, solutions, suspensions, emulsions, or implantable disc.
- the composition will contain from about 0.01 to 99 percent, preferably from about 20 to 75 percent of active compound(s), together with the adjuvants, carriers and/or excipients. While individual needs may vary, determination of optimal ranges of effective amounts of each component is within the skill of the art.
- Typical dosages comprise about 0.01 to about 100 mg/kg body wt.
- the preferred dosages comprise about 0.1 to about 100 mg/kg body wt.
- the most preferred dosages comprise about 1 to about 100 mg/kg body wt.
- Treatment regimen for the administration of the compounds of the present invention can also be determined readily by those with ordinary skill in art. That is, the frequency of administration and size of the dose can be established by routine optimization, preferably while minimizing any side effects.
- the solid unit dosage forms can be of the conventional type.
- the solid form can be a capsule and the like, such as an ordinary gelatin type containing the compounds of the present invention and a carrier, for example, lubricants and inert fillers such as, lactose, sucrose, or cornstarch.
- these compounds are tabulated with conventional tablet bases such as lactose, sucrose, or cornstarch in combination with binders like acacia, cornstarch, or gelatin, disintegrating agents, such as cornstarch, potato starch, or alginic acid, and a lubricant, like stearic acid or magnesium stearate.
- the tablets, capsules, and the like can also contain a binder such as gum tragacanth, acacia, corn starch, or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, lactose, or saccharin.
- a binder such as gum tragacanth, acacia, corn starch, or gelatin
- excipients such as dicalcium phosphate
- a disintegrating agent such as corn starch, potato starch, alginic acid
- a lubricant such as magnesium stearate
- a sweetening agent such as sucrose, lactose, or saccharin.
- a liquid carrier such as a fatty oil.
- tablets can be coated with shellac, sugar, or both.
- a syrup can contain, in addition to active ingredient, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye, and flavoring such as cherry or orange flavor.
- these active compounds can be incorporated with excipients and used in the form of tablets, capsules, elixirs, suspensions, syrups, and the like.
- Such compositions and preparations should contain at least 0.1% of active compound.
- the percentage of the compound in these compositions can, of course, be varied and can conveniently be between about 2% to about 60% of the weight of the unit.
- the amount of active compound in such therapeutically useful compositions is such that a suitable dosage will be obtained.
- Preferred compositions according to the present invention are prepared so that an oral dosage unit contains between about 1 mg and 800 mg of active compound.
- the active compounds of the present invention may be orally administered, for example, with an inert diluent, or with an assailable edible carrier, or they can be enclosed in hard or soft shell capsules, or they can be compressed into tablets, or they can be incorporated directly with the food of the diet.
- the pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions.
- the form should be sterile and should be fluid to the extent that easy syringability exists. It should be stable under the conditions of manufacture and storage and should be preserved against the contaminating action of microorganisms, such as bacteria and fungi.
- the carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils.
- the compounds or pharmaceutical compositions of the present invention may also be administered in injectable dosages by solution or suspension of these materials in a physiologically acceptable diluent with a pharmaceutical adjuvant, carrier or excipient.
- a pharmaceutical adjuvant, carrier or excipient include, but are not limited to, sterile liquids, such as water and oils, with or without the addition of a surfactant and other pharmaceutically and physiologically acceptable components.
- Illustrative oils are those of petroleum, animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, or mineral oil.
- water, saline, aqueous dextrose and related sugar solution, and glycols, such as propylene glycol or polyethylene glycol, are preferred liquid carriers, particularly for injectable solutions.
- the pharmaceutical forms suitable for implantable use include sterile wafers of polycarboxyphenoxypropane-sebacic-acid (pCPP:SA) polymers, poly(D,L-lactic acid), polyhydroxybutyrate, lysine diisocyanate (LDI)-glycerol polyurethane, and poly(D-L lactide-co-glycolide).
- pCPP:SA polycarboxyphenoxypropane-sebacic-acid
- LKI lysine diisocyanate
- the form should be sterile and should be a wafer or disc of suitable dimensions for surgical implantation in the brain.
- the polymers should be stable under the conditions of manufacture and storage and should be preserved against the contaminating action of microorganisms, such as bacteria and fungi.
- the wafers should be biodegradable in the central nervous system, and should permit the slow release of the above mentioned compounds, ranging from 24 hours up to 6 months. Such wafers may be of particular value in enhancing the success of temporal lobe epilepsy surgery by suppressing persistent epileptogenic structures.
- the invention provides compounds and compositions, including any aspect described herein, for use in any of the methods of this invention.
- use of a compound of this invention or a composition comprising the same will have utility in inhibiting, suppressing, enhancing or stimulating a desired response in a subject, as will be understood by one skilled in the art.
- the compositions may further comprise additional active ingredients, whose activity is useful for the particular application for which the compound of this invention is being administered.
- compositions typically must be sterile and stable under the conditions of manufacture and storage.
- the composition can be formulated as a solution, microemulsion, liposome, or other ordered structure suitable to high drug concentration.
- the carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof.
- the proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants.
- isotonic agents for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the composition.
- Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, monostearate salts and gelatin.
- the modulators can be administered in a time release formulation, for example in a composition which includes a slow release polymer.
- the active compounds can be prepared with carriers that will protect the compound against rapid release, such as a controlled release formulation, including implants and microencapsulated delivery systems.
- Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, polylactic acid and polylactic, polyglycolic copolymers (PLG). Many methods for the preparation of such formulations are patented or generally known to those skilled in the art.
- the mode of administration may be oral, for intestinal delivery; intranasal, for nasal delivery; and intravenous for delivery through the blood-brain barrier.
- Other modes of administration as are known in the art may also be used, including, but not limited to intrathecal, intramuscular, intrabronchial, intrarectal, intraocular, and intravaginal delivery,
- the modulator compounds can be administered as oral dosage compositions for small intestinal delivery.
- Such oral dosage compositions for small intestinal delivery are well-known in the art, and generally comprise gastroresistent tablets or capsules (Remington's Pharmaceutical Sciences, 16th Ed., Eds. Osol, Mack Publishing Co., Chapter 89 (1980); Digenis et al, J. Pharm. Sci., 83:915-921 (1994); Vantini et al, Clinica Terapeutica, 145:445-451 (1993); Yoshitomi et al, Chem. Pharm.
- Tablets are made gastroresistent by the addition of compounds such as cellulose acetate phthalate or cellulose acetate terephthalate.
- Capsules are solid dosage forms in which the modulator compound is enclosed in either a hard or soft, soluble container or shell of gelatin.
- the gelatin used in the manufacture of capsules is obtained from collagenous material by hydrolysis. There are two types of gelatin. Type A, derived from pork skins by acid processing, and Type B, obtained from bones and animal skins by alkaline processing.
- Type A derived from pork skins by acid processing
- Type B obtained from bones and animal skins by alkaline processing.
- the use of hard gelatin capsules permit a choice in prescribing a modulator compound or a combination thereof at the exact dosage level considered best for the individual subject.
- the hard gelatin capsule consists of two sections, one slipping over the other, thus completely surrounding the modulator compound.
- These capsules are filled by introducing the modulator compound, or gastroresistent beads containing the modulator compound, into the longer end of the capsule, and then slipping on the cap.
- Hard gelatin capsules are made largely from gelatin, FD&C colorants, and sometimes an opacifying agent, such as titanium dioxide.
- the USP permits the gelatin for this purpose to contain 0.15% (w/v) sulfur dioxide to prevent decomposition during manufacture.
- oral dosage compositions for small intestinal delivery also include liquid compositions which contain aqueous buffering agents that prevent the modulator compound from being significantly inactivated by gastric fluids in the stomach, thereby allowing the modulator compound to reach the small intestines in an active form.
- aqueous buffering agents which can be employed in the present invention include bicarbonate buffer (pH 5.5 to 8.7, preferably about pH 7.4).
- the oral dosage composition is a liquid composition
- the composition be prepared just prior to administration so as to minimize stability problems.
- the liquid composition can be prepared by dissolving lyophilized modulator compound in the aqueous buffering agent.
- Oral dosage compositions for small intestinal delivery also include liquid compositions which may optionally contain aqueous buffering agents that prevent the therapeutic agent and modulator compound from being significantly inactivated by gastric fluids in the stomach, thereby allowing the biologically active ingredient and modulator compound to reach the small intestines in an active form.
- aqueous buffering agents which can be employed in the present invention include bicarbonate buffer (pH 5.5 to 8.7, preferably about pH 7.4).
- the oral dosage composition is a liquid composition
- the composition be prepared just prior to administration so as to minimize stability problems.
- the liquid composition can be prepared by dissolving lyophilized therapeutic agent and modulator compound in the aqueous buffering agent.
- Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization.
- dispersions are prepared by incorporating the active compound into a sterile vehicle which contains a basic dispersion medium and the required other ingredients from those enumerated above.
- the preferred methods of preparation are vacuum drying and freeze-drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.
- a “nasal” delivery composition differs from an “intestinal” delivery composition in that the latter must have gastroresistent properties in order to prevent the acidic degradation of the active agents in the stomach, whereas the former generally comprises water-soluble polymers with a diameter of about 50 ⁇ m order to reduce the mucociliary clearance, and to achieve a reproducible bioavailability of the nasally administered agents.
- An “intravenous” delivery composition differs from both the “nasal” and “intestinal” delivery compositions in that there is no need for gastroresistance or water-soluble polymers in the “intravenous” delivery composition.
- Nasal dosage compositions for nasal delivery are well-known in the art.
- Such nasal dosage compositions generally comprise water-soluble polymers that have been used extensively to prepare pharmaceutical dosage forms (Martin et al, In: Physical Chemical Principles of 20 Pharmaceutical Sciences, 3rd Ed., pages 592-638 (1983)) that can serve as carriers for peptides for nasal administration (Davis, In: Delivery Systems for Peptide Drugs, 125:1-21 (1986)).
- the nasal absorption of pap tides embedded in polymer matrices has been shown to be enhanced through retardation of nasal mucociliary clearance (Illum et al, Int. J. Pharm., 46:261-265 (1988).
- microparticles with a diameter under 10 pm can escape the filtering system of the nose and deposit in the lower airways. Microparticles larger than 200 pm in diameter will not be retained in the nose after nasal administration (Lewis et al, Proc. Int. Symp. Control Rel. Bioact. Mater., 17:280-290 (1990)).
- the particular water-soluble polymer employed is not critical to the present invention, and can be selected from any of the well-known water-soluble polymers employed for nasal dosage forms.
- a typical example of a water-soluble polymer useful for nasal delivery is polyvinyl alcohol (pvA).
- pvA polyvinyl alcohol
- This material is a swellable hydrophilic polymer whose physical properties depend on the molecular weight, degree of hydrolysis, cross-linking density, and crystallinity (Peppas et al, In: Hydrogels in Medicine and Pharmacy, 3:109′131(1987).
- PYA can be used in the coating of dispersed materials through phase separation, spray-drying, spray-embedding, and spray-densation (Ting et al, supra).
- a “skin” delivery composition comprising a modulator compound of the invention may include in addition a therapeutic or immunogenic agent, fragrance, creams, ointments, colorings, and other compounds so long as the added component does not deleteriously affect transdermal delivery of the therapeutic or immunogenic agent.
- Conventional pharmaceutically acceptable emulsifiers, surfactants, suspending agents, antioxidants, osmotic enhancers, extenders, diluents and preservatives may also be added.
- Water soluble polymers can also be used as carriers.
- the particular therapeutic or immunogenic agent employed is not critical to the present invention, and can be, e.g., any drug compound, biologically active peptide, vaccine, or any other moiety otherwise not absorbed through the transcellular pathway, regardless of size or charge.
- the amount of active compound in the composition may vary according to factors such as the disease state, age, sex, and weight of the individual. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, a single bolus may be administered, several divided doses may be administered over time or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It is especially advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage.
- Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the mammalian subjects to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier.
- the specification for the dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such an active compound for the treatment of sensitivity in individuals.
- pharmaceutically-acceptable carrier includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible.
- the carrier is suitable for parenteral administration.
- a carrier may be suitable for administration into the central nervous system (e.g., intraspinally or intracerebrally).
- the carrier can be suitable for intravenous, intraperitoneal, or intramuscular administration.
- the carrier is suitable for oral administration.
- Pharmaceutically-acceptable carriers include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion.
- Infrared (IR) spectra for the compounds were recorded in KBr discs on a Mattson Satellite FTIR in cm ⁇ 1 .
- 1 H and 13 C spectra were recorded in DMSO-d, on a Bruker Avance III DPX 300 MHz instrument.
- 19 F spectra were recorded in DMSO d 6 on a Bruker Avance III 600 (564.6 mHz). Chemical shifts were expressed in parts per million with tetramethylsilane as internal standard.
- Mass spectrometry was performed on a Thermo Scientific LTQ-FT at the University of Cincinnati Mass. Spectrometry facility.
- the purity of the compounds was monitored by HPLC using a Waters 2695 separation module and a 2487 dual A absorbance detector with a NovaPak C18 4 ⁇ m 3.9 xl 50 mm column.
- the mobile phases consisted of acetonitrile/H20 using a 30 minute gradient. All compounds were 2:95%.
- Log S, Log P, Log BBB, human intestinal absorption, p-glycoprotein category, CYP 2C9 pKi, hERG pIC50, CYP 2D 6 affinity category, oral CNS score, IV CNS score, MW, flexibility, and total polar surface area were calculated using StarDrop 5.1.1 release Build 178.
- FIGS. 3 , 4 , 5 , 6 , and 7 illustrate the mechanism of action and synthetic reactions used to prepare unlabeled or isotopically stabilized tetronimide modulator compounds comprising one or more deuterium atoms.
- FIG. 4 illustrates the mechanism of action of tetronimide modulating compounds.
- Deuterium can stabilize a stereo-center, or can be used to slow down or suppress metabolism.
- Compound #2066 has a deuterium at the stereocenter, as well as two deuteriums at the benzylic position adjacent to the “C” ring.
- Compound #2084 has two deuteriums on the amino of the tetronimide ring.
- Compound #2085 has a deuterium at the stereocenter, two deuteriums at the benzylic position adjacent to the “C” ring, and two deuteriums on the amino of the tetronimide ring.
- Compound #1072 has two deuteriums at the benzylic position adjacent to the “C” ring, and the “C” ring is perdeuterated.
- Compound #2087 is deuterated at the stereocenter, the benzylic position adjacent to the “C” ring, two deuteriums on the amine of the tetronimide, and the “C” ring is perdeuterated.
- Compound #1084 has the “A” ring perdeuterated.
- FIG. 5 illustrates the synthesis of non-deuterated ASPH modulators in Scheme 1.
- Scheme 2 illustrates the synthesis of compounds of the formula ⁇ I-A ⁇ and ⁇ I-B ⁇ .
- Scheme 3 illustrates the synthesis of compounds of the formula ⁇ I-D ⁇
- Scheme 4 illustrates the synthesis of compounds of the formula ⁇ I-E ⁇ .
- FIG. 6 illustrates an alternate synthesis of compounds of the formula ⁇ I-D ⁇ in Scheme 5.
- Scheme 6 illustrates the synthesis of perdeuterated phenylmethanesulfonyl chloride.
- Scheme 7 illustrates the synthesis of compounds of the formula ⁇ I-F ⁇ .
- FIG. 7 illustrates the synthesis of compounds of the formula ⁇ I-G ⁇ in Scheme 8.
- Scheme 9 illustrates the synthesis of compounds of the formula ⁇ I-G ⁇ .
- Scheme 10 illustrates the synthesis of compounds of the formula ⁇ I-H ⁇ .
- FIGS. 10 - 1 to 10 - 62 illustrate NMR spectra of unlabeled precursor compounds, particularly multiple peaks for specific compounds, each compound given an MO-I number, which can be cross-correlated with current numbers, names, and structures of the #1000 series of compounds listed in Table 3.
- Table 1 is a non-limiting list of unsubstituted and substituted aryl functional groups that can be incorporated into compounds of the invention represented by Formulas noted within the text and embedded or supplemental tables of the specification, the figures, and the claims.
- Table 2 provides a list illustrating the structures, names, and numbers of a variety of key compounds disclosed in this example.
- Sulfonylated compounds are prepared according to U.S. Pat. No. 9,771,356.
- the first eluting enantiomer 1 of 1-d 3 had a ( ⁇ ) optical rotation, whereas the second eluting enantiomer 2 of 1-d 3 had a (+) optical rotation according to additional chiral laser polarimeter detection in the chiral HPLC.
- a sample of 1.07 mmoles rac-1084 is stirring in 10 mL of CF 3 CO 2 D at room temperature. After 1 day the reaction is frozen, and concentrated under reduced pressure. The sample is resuspending in THF, and is stirring in 10 mL of THF in the presence of 4.69 mmoles K 2 CO 3 and 2 mL D 2 O at room temperature. After 9 days the reaction is concentrated under reduced pressure. Preparative chiral HPLC separation of enantiomers of 2089-d 7 is performed to yield 2089(S) and 2089(R). Fractions are collected at ⁇ 78° C. (dry-ice cooling) to prevent racemization. Evaporation under reduced pressure affords the product as white solids.
- Exemplary compounds are typically incubated with human, dog, cat, mouse, rat, or monkey liver or intestinal microsomes under standard reaction conditions. Two samples from each reaction mixture are taken at time intervals, such as 0, 15, 30, 45 and 60 minutes and injected onto an HPLC column to detect and quantify the absolute and/or relative levels of the unmetabolized compound. The Clint and the half-life for each molecule are calculated. Reference compounds for direct comparison include imipramine, propranolol, terfenadine, and verapamil.
- Metabolic stability was performed by a commercial laboratory using a standard protocol.
- Compounds #1066, #2066, #2066(R), and #2066(S) were diluted to 1E-7 M, and incubated with human liver microsomes, or mouse liver microsomes (0.1 mg/mL), and quantified by HPLC.
- Control compounds were imipramine, propranolol, terfenadine and verapamil, which behaved normally as expected.
- Metabolic stability expressed as percent of the parent compound remaining, was calculated by comparing the peak area of the compound at the time point relative to that at time at 0, 15, 30, 45 and 60 minutes.
- the half-life (T1 ⁇ 2) was estimated from the slope of the initial linear range of the logarithmic curve of compound remaining (%) vs. time, assuming the first-order kinetics.
- the apparent intrinsic clearance (CLint, in ⁇ L/min/pmol, ⁇ L/min/mg or ⁇ L/min/Mcell) was calculated.
- FIG. 8 illustrates the activities of undeuterated, racemic, and deuterated enantiomers of tetronimide modulator compounds against ASPH in liver microsome assays.
- FIG. 9 illustrates the activities of specific compounds #1066, #2066(R), and #2066(S) against MCF-7 Cells In Vitro.
- mice such as strains BALB/cJ or C57BL/6NJ or NOD SCID are divided into 6 groups of 5 mice per compound, one group for untreated, one group for vehicle control, one group for undeuterated compound (for example, #1066), one group for racemic deuterated (for example, #2066), one group for (R) isomer deuterated compound (for example, #2066(R)), and one group for (S) deuterated compound (for example, #2066(S)).
- the selected mouse strain is injected with a cancer cell line (such as osteosarcoma, mammary carcinoma, ovarian carcinoma, hepatocellular carcinoma, glioblastoma multiform, neuroblastoma, pancreatic adenocarcinoma, and cholangiocarcinoma cells) that is ASPH positive into the right flank subcutaneously. Untreated animals are left untreated. Vehicle control mice are administered Size “M” capsules containing only lactose daily. Mice in the undeuterated compound group are administered undeuterated compound triturated with lactose at 10 mg/kg in a Size “M” capsule daily.
- a cancer cell line such as osteosarcoma, mammary carcinoma, ovarian carcinoma, hepatocellular carcinoma, glioblastoma multiform, neuroblastoma, pancreatic adenocarcinoma, and cholangiocarcinoma cells
- Deuterated racemic compound group is administered racemic deuterated compound triturated with lactose a 10 mg/kg in a Size “M” capsule daily.
- Mice in the (R) deuterated group are administered the (R) deuterated compound 10 mg/kg that has been triturated with lactose and packaged into a Size “M” capsule daily.
- Mice in the (S) deuterated group are administered the (S) deuterated compound 10 mg/kg that has been triturated with lactose and packaged into a Size “M” capsule daily.
- the size of the tumor is being measured daily, either until death or until day 30 when all animals are sacrificed. Tumors are being excised upon animal death or sacrifice, all tumors are weighed, and metastasis are being counted. At the time of death or sacrifice, animal blood is collected, and blood or serum cholesterol, complement activity, blood coagulation parameters (INR, aPTT) and liver enzymes (ALT, AST and GGT) are quantified.
- journal articles and patent documents All references, as journal articles or patent documents (published applications or issued patents), cited herein, are incorporated by reference in their entirety, as if written herein.
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Abstract
Description
peptide-L-aspartate+2-oxoglutarate+O2⇄peptide-3-hydroxy-L-aspartate+succinate+CO2 (Reaction 1)
or a salt, ester, metabolite, prodrug, or solvate thereof, wherein V1 is deuterium (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
or a salt, ester, metabolite, prodrug, or solvate thereof, wherein at least one of V1, V2, and V3 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance;
or a salt, ester, metabolite, prodrug, or solvate thereof, wherein at least one of V1, V2, V3, or Z1, Z2, Z3, Z4, and Z5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
or a salt, ester, metabolite, prodrug, or solvate thereof, wherein at least one of V4 or V5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
or a salt, ester, metabolite, prodrug, or solvate thereof, wherein at least one of V1, V2, V3, V4, or V5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
or a salt, ester, metabolite, prodrug, or solvate thereof, wherein at least one of V2, V3, or Z1, Z2, Z3, Z4, or Z5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
or a salt, ester, metabolite, prodrug, or solvate thereof, wherein at least one of V1, V2, V3, V4, V5, or Z1, Z2, Z3, Z4, Z5 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
or a salt, ester, metabolite, prodrug, or solvate thereof, wherein at least one of V2, V3, Z1, Z2, Z3, Z4, Z5, Z6, Z7, Z8, or Z9 is a deuterium atom (D) and any atom not designated as deuterium is present as hydrogen (H, or not shown) at its natural isotopic abundance.
- 2001 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d methanesulfonate-d3;
- 2001(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d methanesulfonate-d3;
- 2001(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d methanesulfonate-d3;
- 2002 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d ethane-1-sulfonate-1,1-d2;
- 2002(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d ethane-1-sulfonate-1,1-d2;
- 2002(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d ethane-1-sulfonate-1,1-d2;
- 2003 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d propane-1-sulfonate-1,1-d2;
- 2003(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d propane-1-sulfonate-1,1-d2;
- 2003(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d propane-1-sulfonate-1,1-d2;
- 2004 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d propane-2-sulfonate-2-d;
- 2004(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d propane-2-sulfonate-2-d;
- 2004(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d propane-2-sulfonate-2-d;
- 2005 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d butane-1-sulfonate-1,1-d2;
- 2005(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d butane-1-sulfonate-1,1-d2;
- 2005(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d butane-1-sulfonate-1,1-d2;
- 2006 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d 2-methylpropane-1-sulfonate-1,1-d2;
- 2006(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d 2-methylpropane-1-sulfonate-1,1-d2;
- 2006(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d 2-methylpropane-1-sulfonate-1,1-d2;
- 2007 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d benzenesulfonate;
- 2007(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d benzenesulfonate;
- 2007(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d benzenesulfonate;
- 2008 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2008(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2008(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2009 2-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2009(R) (R)-2-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2009(S) (S)-2-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2010 2-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2010(R) (R)-2-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2010(S) (S)-2-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2011 2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2011(R) (R)-2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2011(S) (S)-2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2012 2-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2012(R) (R)-2-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2012(S) (S)-2-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2013 2-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2013(R) (R)-2-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2013(S) (S)-2-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2014 2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2014(R) (R)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2014(S) (S)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2015 2-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2015(R) (R)-2-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2015(S) (S)-2-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2016 methyl 3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2016(R) methyl (R)-3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2016(S) methyl (S)-3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2017 methyl 4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2017(R) methyl (R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2017(S) methyl (S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2018 methyl 4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2018(R) methyl (R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2018(S) methyl (S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2019 ethyl 4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2019(R) ethyl (R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2019(S) ethyl (S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2020 5-(4-acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2020(R) (R)-5-(4-acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2020(S) (S)-5-(4-acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2021 2-amino-5-(4-carbamoylphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2021(R) (R)-2-amino-5-(4-carbamoylphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2021(S) (S)-2-amino-5-(4-carbamoylphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2022 4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2022(R) (R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2022(S) (S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2023 sodium 4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2023(R) sodium (R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2023(S) sodium (S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2024 potassium 4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2024(R) potassium (R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2024(S) potassium (S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2027 2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2027(R) (R)-2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2027(S) (S)-2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2028 2-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2028(R) (R)-2-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2028(S) (S)-2-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2029 2-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2029(R) (R)-2-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2029(S) (S)-2-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2030 2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2030(R) (R)-2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2030(S) (S)-2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2031 2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2031(R) (R)-2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2031(S) (S)-2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2032 2-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2032(R) (R)-2-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2032(S) (S)-2-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2033 2-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2033(R) (R)-2-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2033(S) (S)-2-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2034 2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2034(R) (R)-2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2034(S) (S)-2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2035 2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2035(R) (R)-2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2035(S) (S)-2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2036 2-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2036(R) (R)-2-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2036(S) (S)-2-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2037 2-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2037(R) (R)-2-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2037(S) (S)-2-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2038 2-amino-5-(4-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2038(R) (R)-2-amino-5-(4-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2038(S) (S)-2-amino-5-(4-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2039 2-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2039(R) (R)-2-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2039(S) (S)-2-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2040 2-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2040(R) (R)-2-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2040(S) (S)-2-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2041 2-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2041(R) (R)-2-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2041(S) (S)-2-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2042 2-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2042(R) (R)-2-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2042(S) (S)-2-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2043 2-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2043(R) (R)-2-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2043(S) (S)-2-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2044 2-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2044(R) (R)-2-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2044(S) (S)-2-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2045 2-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2045(R) (R)-2-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2045(S) (S)-2-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2046 2-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2046(R) (R)-2-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2046(S) (S)-2-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2047 2-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2047(R) (R)-2-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2047(S) (S)-2-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2048 2-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2048(R) (R)-2-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2048(S) (S)-2-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2049 2-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2049(R) (R)-2-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2049(S) (S)-2-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2050 2-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2050(R) (R)-2-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2050(S) (S)-2-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2051 2-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2051(R) (R)-2-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2051(S) (S)-2-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2052 2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2052(R) (R)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2052(S) (S)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2053 2-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2053(R) (R)-2-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2053(S) (S)-2-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2054 2-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2054(R) (R)-2-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2054(S) (S)-2-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2055 2-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2055(R) (R)-2-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2055(S) (S)-2-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2056 2-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2056(R) (R)-2-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2056(S) (S)-2-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2057 2-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2057(R) (R)-2-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2057(S) (S)-2-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2058 2-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2058(R) (R)-2-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2058(S) (S)-2-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2059 2-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2059(R) (R)-2-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2059(S) (S)-2-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2060 2-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2060(R) (R)-2-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2060(S) (S)-2-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2061 2-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2061(R) (R)-2-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2061(S) (S)-2-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2062 2-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2062(R) (R)-2-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2062(S) (S)-2-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2063 2-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2063(R) (R)-2-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2063(S) (S)-2-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2064 2-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2064(R) (R)-2-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2064(S) (S)-2-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2065 2-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2065(R) (R)-2-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2065(S) (S)-2-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2066 2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2066(R) (R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2066(S) (S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2067 2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4-fluorophenyl)methanesulfonate-d2;
- 2067(R) (R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4-fluorophenyl)methanesulfonate-d2;
- 2067(S) (S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4-fluorophenyl)methanesulfonate-d2;
- 2068 methyl 4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2068(R) methyl (R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2068(S) methyl (S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2069 ethyl 4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2069(R) ethyl (R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2069(S) ethyl (S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2070 4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2070(R) (R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2070(S) (S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2071 methyl 4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2071(R) methyl (R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2071(S) methyl (S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2072 2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2072(R) (R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2072(S) (S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2073 methyl 4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2073(R) methyl (R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2073(S) methyl (S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2074 ethyl 4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2074(R) ethyl (R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2074(S) ethyl (S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2075 4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2075(R) (R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2075(S) (S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoic acid-d;
- 2076 methyl 4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2076(R) methyl (R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2076(S) methyl (S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2077 2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2077(R) (R)-2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2077(S) (S)-2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2078 2-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2078(R) (R)-2-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2078(S) (S)-2-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2079 methyl 2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)phenyl)acetate-d2;
- 2079(R) methyl (R)-2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)phenyl)acetate-d2;
- 2079(S) methyl (S)-2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)phenyl)acetate-d2;
- 2080 2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2080(R) (R)-2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2080(S) (S)-2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2081 2-amino-4-oxo-5-(6-(trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2081(R) (R)-2-amino-4-oxo-5-(6-(trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2081(S) (S)-2-amino-4-oxo-5-(6-(trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2082 2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4-chlorophenyl)methanesulfonate-d2;
- 2082(R) (R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4-chlorophenyl)methanesulfonate-d2;
- 2082(S) (S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4-chlorophenyl)methanesulfonate-d2;
- 2083 2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4-(trifluoromethyl)phenyl)methanesulfonate-d2;
- 2083(R) (R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4-(trifluoromethyl)phenyl)methanesulfonate-d2;
- 2084 2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl phenylmethanesulfonate;
- 2085 2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2085(R) (R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2085(S) (S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2086 2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl (phenyl-d5)methanesulfonate;
- 2087 2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2087(R) (R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2087(S) (S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2088 2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl phenylmethanesulfonate;
- 2089 2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2089(R) (R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2089(S) (S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2090 2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2090(R) (R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2090(S) (S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2091 2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl (phenyl-d5)methanesulfonate;
- 2092 2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2092(R) (R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2092(S) (S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2093 2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2;
- 2093(R) (R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2; and
- 2093(S) (S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2.
- 2008 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2008(R) (R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2008(S) (S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2014 2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2014(R) (R)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2014(S) (S)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2017 methyl 4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2017(R) methyl (R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2017(S) methyl (S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;
- 2018 methyl 4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2018(R) methyl (R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2018(S) methyl (S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;
- 2052 2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2052(R) (R)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2052(S) (S)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2066 2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2066(R) (R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
- 2066(S) (S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2;
TABLE 1 |
A Non-Limiting List of Aryl Functional Groups That Can Be Incorporated Formulas of the Invention |
Functional | ||
Group | ||
No | Structure | Aryl Name |
a |
|
phenyl |
b |
|
2-fluorophenyl |
c |
|
3-fluorophenyl |
d |
|
4-fluorophenyl |
e |
|
2-chlorophenyl |
f |
|
3-chlorophenyl |
g |
|
4-chlorophenyl |
h |
|
2-bromophenyl |
i |
|
3-bromophenyl |
j |
|
4-bromophenyl |
k |
|
2-iodophenyl |
l |
|
3-iodophenyl |
m |
|
4-iodophenyl |
n |
|
2-trifluoromethylphenyl |
o |
|
3-trifluoromethylphenyl |
p |
|
4-trifluoromethylphenyl |
q |
|
2-benzoic acid |
r |
|
3-benzoic acid |
s |
|
4-benzoic acid |
t |
|
2-carboxymethylphenyl |
u |
|
3-carboxymethylphenyl |
v |
|
4-carboxymethylphenyl |
w |
|
2-methoxyphenyl |
x |
|
3-methoxyphenyl |
y |
|
4-methoxyphenyl |
z |
|
2-carboxyethylphenyl |
aa |
|
3-carboxyethylphenyl |
ab |
|
4-carboxyethylphenyl |
ac |
|
2-nitrilephenyl |
ad |
|
3-nitrilephenyl |
ae |
|
4-nitrilephenyl |
af |
|
2-sulfonamidophenyl |
ag |
|
3-sulfonamidophenyl |
ah |
|
4-sulfonamidophenyl |
ai |
|
2,3-difluorophenyl |
aj |
|
2,4-difluorophenyl |
ak |
|
2,5-difluorophenyl |
al |
|
2,6-difluorophenyl |
am |
|
3,4-difluorophenyl |
an |
|
3,5-difluorophenyl |
ap |
|
2,3-dichlorophenyl |
aq |
|
2,4-dichlorophenyl |
ar |
|
2,5-dichlorophenyl |
as |
|
2,6-dichlorophenyl |
at |
|
3,4-dichlorophenyl |
au |
|
3,5-dichlorophenyl |
av |
|
2-chloro-3-fluorophenyl |
aw |
|
2-chloro-4-fluorophenyl |
ax |
|
2-chloro-5-fluorophenyl |
ay |
|
2-chloro-6-fluorophenyl |
az |
|
3-chloro-2-fluorophenyl |
ba |
|
3-chloro-4-fluorophenyl |
bb |
|
3-chloro-5-fluorophenyl |
bc |
|
3-chloro-6-fluorophenyl |
bd |
|
4-chloro-2-fluorophenyl |
be |
|
4-chloro-3-fluorophenyl |
bf |
|
2,3-methylenedioxyphenyl |
bg |
|
3,4-methylenedioxyphenyl |
bh |
|
2,3-difluoromethylenedioxyphenyl |
bi |
|
3,4-difluoromethylenedioxyphenyl |
bj |
|
Methyl-phenyl acetate |
bk |
|
N-2-phenyl-methanesulfonamide |
bl |
|
N-3-phenyl-methanesulfonamide |
bm |
|
N-4-phenyl-methanesulfonamide |
bn |
|
2-acetylphenyl |
bo |
|
3-acetylphenyl |
bp |
|
4-acetylphenyl |
bq |
|
4-carboxymethyl-2-fluorophenyl |
br |
|
4-carboxymethyl-3-fluorophenyl |
bs |
|
4-carboxymethyl-2,3-difluorophenyl |
bt |
|
4-carboxymethyl-3,5-difluorophenyl |
bu |
|
4-carboxymethyl-2,3,5-trifluorophenyl |
bv |
|
4-carboxymethyl-2,3,5,6-tetrafluorophenyl |
bw |
|
4-carboxymethyl-2-chlorophenyl |
bx |
|
4-carboxymethyl-3-chlorophenyl |
by |
|
4-carboxymethyl-3-chloro-2-fluorophenyl |
bz |
|
4-carboxymethyl-2-chloro-3-fluorophenyl |
ca |
|
4-carboxymethyl-3-chloro-5-fluorophenyl |
cb |
|
4-carboxymethyl-2-methoxyphenyl |
cc |
|
4-carboxymethyl-3-methoxyphenyl |
cd |
|
4-carboxymethyl-2-bromophenyl |
ce |
|
4-carboxymethyl-3-bromophenyl |
cf |
|
2-fluoro-4-benzoic acid |
cg |
|
3-fluoro-4-benzoic acid |
ch |
|
2,3-difluoro-4-benzoic acid |
ci |
|
3,5-difluoro-4-benzoic acid |
cj |
|
2,3,5-trifluoro-4-benzoic acid |
ck |
|
2,3,5,6-tetrafluoro-4-benzoic acid |
cl |
|
2-chloro-4-benzoic acid |
cm |
|
3-chloro-4-benzoic acid |
cn |
|
3-chloro-2-fluoro-4-benzoic acid |
co |
|
2-chloro-3-fluoro-4-benzoic acid |
cp |
|
3-chloro-5-fluoro-4-benzoic acid |
cq |
|
2-methoxy-4-benzoic acid |
cr |
|
3-methoxy-4-benzoic acid |
cs |
|
2-bromo-4-benzoic acid |
ct |
|
3-bromo-4-benzoic acid |
TABLE 2 |
(#1001-1083) |
Structures, Names, and Numbers of Key Unlabeled Compounds Listed in Example 1 |
CP # | Structure | Name | Formula | MW |
1001 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl methanesulfonate | C11H10ClNO5S | 303.71 |
1002 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl ethanesulfonate | C12H12ClNO5S | 317.74 |
1003 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl propane-1-sulfonate | C13H14ClNO5S | 331.77 |
1004 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl propane-2-sulfonate | C13H14ClNO5S | 331.77 |
1005 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl butane-1-sulfonate | C14H16ClNO5S | 345.79 |
1006 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl 2-methylpropane-1- sulfonate | C14H16ClNO5S | 345.79 |
1008 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14ClNO5S | 379.81 |
1009 |
|
2-amino-5-(2-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14ClNO5S | 379.81 |
1010 |
|
2-amino-5-(3-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14ClNO5S | 379.81 |
1011 |
|
2-amino-5-(2,3- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13Cl2NO5S | 414.25 |
1012 |
|
2-amino-5-(2,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13Cl2NO5S | 414.25 |
1013 |
|
2-amino-5-(2,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13Cl2NO5S | 414.25 |
1014 |
|
2-amino-5-(3,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13Cl2NO5S | 414.25 |
1015 |
|
2-amino-5-(3,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13Cl2NO5S | 414.25 |
1016 |
|
methyl 3-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2- yl)benzoate | C19H17NO7S | 403.40 |
1017 |
|
methyl 4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2- yl)benzoate | C19H17NO7S | 403.40 |
1018 |
|
methyl 4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2-yl)-2- fluorobenzoate | C19H16FNO7S | 421.40 |
1019 |
|
ethyl 4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2- yl)benzoate | C20H19NO7S | 417.43 |
1020 |
|
5-(4-acetylphenyl)-2-amino- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C19H17NO6S | 387.41 |
1021 |
|
2-amino-5-(4- carbamoylphenyl)-4-oxo- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H16N2O6S | 388.39 |
1022 |
|
4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2- yl)benzoic acid | C18H15NO7S | 389.38 |
1027 |
|
2-amino-5-(2-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14FNO5S | 363.36 |
1028 |
|
2-amino-5-(3-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14FNO5S | 363.36 |
1029 |
|
2-amino-5-(4-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14FNO5S | 363.36 |
1030 |
|
2-amino-5-(2,3- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1031 |
|
2-amino-5-(2,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1032 |
|
2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1033 |
|
2-amino-5-(2,6- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1034 |
|
2-amino-5-(3,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1035 |
|
2-amino-5-(3,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1036 |
|
2-amino-5-(2- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H17NO6S | 375.39 |
1037 |
|
2-amino-5-(3- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H17NO6S | 375.39 |
1038 |
|
2-amino-5-(4- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H17NO6S | 375.39 |
1039 |
|
2-amino-5-(2,3- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C19H19NO7S | 405.42 |
1040 |
|
2-amino-5-(2,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C19H19NO7S | 405.42 |
1041 |
|
2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C19H19NO7S | 405.42 |
1042 |
|
2-amino-5-(2,6- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C19H19NO7S | 405.42 |
1043 |
|
2-amino-5-(3,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C19H19NO7S | 405.42 |
1044 |
|
2-amino-5-(3,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C19H19NO7S | 405.42 |
1045 |
|
2-amino-5-(2-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14BrNO5S | 424.27 |
1046 |
|
2-amino-5-(3-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14BrNO5S | 424.27 |
1047 |
|
2-amino-5-(4-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H14BrNO5S | 424.27 |
1048 |
|
2-amino-5-(2-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1049 |
|
2-amino-5-(2-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1050 |
|
2-amino-5-(2-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1051 |
|
2-amino-5-(2-chloro-6- fluorophenyl)-4-oxo-4,5- dihydofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1052 |
|
2-amino-5-(3-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1053 |
|
2-amino-5-(3-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1054 |
|
2-amino-5-(3-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1055 |
|
2-amino-5-(5-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1056 |
|
2-amino-5-(4-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1057 |
|
2-amino-5-(4-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13ClFNO5S | 397.80 |
1058 |
|
2-amino-4-oxo-5-(o-tolyl)- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H17NO5S | 359.40 |
1059 |
|
2-amino-4-oxo-5-(m-tolyl)- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H17NO5S | 359.40 |
1060 |
|
2-amino-4-oxo-5-(p-tolyl)- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H17NO5S | 359.40 |
1061 |
|
2-amino-5-(3-cyanophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H14N2O5S | 370.38 |
1062 |
|
2-amino-5-(4-cyanophenyl)- 4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H14N2O5S | 370.38 |
1063 |
|
2-amino-4-oxo-5-phenyl-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H15NO5S | 345.37 |
1064 |
|
2-amino-4-oxo-5-(2- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H14F3NO5S | 413.37 |
1065 |
|
2-amino-4-oxo-5-(3- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H14F3NO5S | 413.37 |
1066 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H14F3NO5S | 413.37 |
1067 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4- fluorophenyl) methanesulfonate | C18H13F4NO5S | 431.36 |
1068 |
|
methyl 4-(5-amino-4-(((4- fluorobenzyl)sulfonyl)oxy)-3- oxo-2,3-dihydrofuran-2- yl)benzoate | C19H16FNO7S | 421.40 |
1069 |
|
ethyl 4-(5-amino-4-(((4- fluorobenzyl)sulfonyl)oxy)-3- oxo-2,3-dihydrofuran-2- yl)benzoate | C20H18FNO7S | 435.42 |
1070 |
|
4-(5-amino-4-(((4- fluorobenzyl)sulfonyl)oxy)-3- oxo-2,3-dihydrofuran-2- yl)benzoic acid | C18H14FNO7S | 407.37 |
1071 |
|
methyl 4-(5-amino-4-(((4- fluorobenzyl)sulfonyl)oxy)-3- oxo-2,3-dihydrofuran-2-yl)- 2-fluorobenzoate | C19H15F2NO7S | 439.39 |
1077 |
|
2-amino-5- (benzo[d][1,3]dioxol-5-yl)-4- oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H15NO7S | 389.38 |
1078 |
|
2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol- 5-yl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H13F2NO7S | 425.36 |
1079 |
|
methyl 2-(4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2- yl)phenyl)acetate | C20H19NO7S | 417.43 |
1081 |
|
2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3- yl)-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C17H13F3N2O5S | 414.36 |
1082 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4- chlorophenyl) methanesulfonate | C18H13ClF3NO5S | 447.81 |
1083 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4- (trifluoromethyl)phenyl) methanesulfonate | C19H13F6NO5S | 481.37 |
TABLE 3 |
Compounds by Informal Number and Chemical Name with NMR Spectra |
Mol | ||||
CP # | Structure and Informal Name | Chemical Name | Formula | Wt |
1010 |
|
2-amino-5-(3-chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H14ClNO5S | 379.81 |
1029 |
|
2-amino-5-(4-fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H14FNO5S | 363.36 |
1028 |
|
2-amino-5-(3-fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H14FNO5O | 363.36 |
1027 |
|
2-amino-5-(2-fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H14FNO5S | 363.36 |
1030 |
|
2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1034 |
|
2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1031 |
|
2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1035 |
|
2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F2NO5S | 381.35 |
1011 |
|
2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13Cl2NO5S | 414.25 |
1014 |
|
2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13Cl2NO5S | 414.25 |
1062 |
|
2-amino-5-(4-cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H14N2O5S | 370.38 |
1066 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H14F3NO5S | 413.37 |
1047 |
|
2-amino-5-(4-bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H14BrNO5S | 424.27 |
2081 |
|
2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3-yl)-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C17H13F3N2O5S | 414.36 |
1017 |
|
methyl 4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl)benzoate | C19H17NO7S | 403.40 |
1077 |
|
2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4- oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H15NO7S | 389.38 |
1078 |
|
2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo- 4,5-dihydrofuran-3-yl phenylmethanesulfonate | C18H13F2NO7S | 425.36 |
1079 |
|
methyl 2-(4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl)phenyl)acetate | C20H19NO7S | 417.43 |
2082 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4- chlorophenyl)methanesulfonate | C18H13ClF3NO5S | 447.81 |
2067 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4- fluorophenyl)methanesulfonate | C18H13F4NO5S | 431.36 |
2083 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4- (trifluoromethyl)phenyl)methanesulfonate | C19H13F6NO5S | 481.37 |
TABLE 4 |
(Selected #1000 series and #2001-2093) |
Structures, Names, and Numbers of Key Isotopically-Stabilized Tetronimide Compounds Listed in Example 2 |
New # | Structure | Name | Formula | MW |
1007 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl benzenesulfonate-d5 | C16H7D5ClNO5S | 370.81 |
1072 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (phenyl- d5)methanesulfonate-d2 | C18H7D7F3NO5S | 420.41 |
1073 |
|
methyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl)benzoate | C19H10D7NO7S | 410.45 |
1074 |
|
ethyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl)benzoate | C20H12D7NO7S | 424.47 |
1075 |
|
4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl)benzoic acid | C18H8D7NO7S | 396.42 |
1076 |
|
methyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl)-2- fluorobenzoate | C19H9D7FNO7S | 428.44 |
1084 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H10D4F3NO5S | 417.39 |
1085 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl (phenyl- d5)methanesulfonate | C18H5D9F3NO5S | 422.42 |
2001 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d methanesulfonate-d3 | C11H6D4ClNO5S | 307.74 |
2001(R) |
|
(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d methanesulfonate-d3 | C11H6D4ClNO5S | 307.74 |
2001(S) |
|
(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d methanesulfonate-d3 | C11H6D4ClNO5S | 307.74 |
2002 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d ethane-1-sulfonate-1,1- d2 | C12H9D3ClNO5S | 320.76 |
2002(R) |
|
(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d ethane-1-sulfonate-1,1-d2 | C12H9D3ClNO5S | 320.76 |
2002(S) |
|
(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d ethane-1-sulfonate-1,1-d2 | C12H9D3ClNO5S | 320.76 |
2003 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d propane-1-sulfonate-1,1- d2 | C13H11D3ClNO5S | 334.79 |
2003(R) |
|
(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d propane-1-sulfonate-1,1-d2 | C13H11D3ClNO5S | 334.79 |
2003(S) |
|
(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d- propane-1-sulfonate-1,1-d2 | C13H11D3ClNO5S | 334.79 |
2004 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d propane-2-sulfonate-2-d | C13H12D2ClNO5S | 333.78 |
2004(R) |
|
(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d propane-2-sulfonate-2-d | C13H12D2ClNO5S | 333.78 |
2004(S) |
|
(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d propane-2-sulfonate-2-d | C13H12D2ClNO5S | 333.78 |
2005 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d butane-1-sulfonate-1,1- d2 | C14H13D3ClNO5S | 348.81 |
2005(R) |
|
(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d butane-1-sulfonate-1,1-d2 | C14H13D3ClNO5S | 348.81 |
2005(S) |
|
(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d butane-1-sulfonate-1,1-d2 | C14H13D3ClNO5S | 348.81 |
2006 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d 2-methylpropane-1- sulfonate-1,1-d2 | C14H13D3ClNO5S | 348.81 |
2006(R) |
|
(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d 2- methylpropane-1-sulfonate- 1,1-d2 | C14H13D3ClNO5S | 348.81 |
2006(S) |
|
(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d 2- methylpropane-1-sulfonate- 1,1-d2 | C14H13D3ClNO5S | 348.81 |
2007 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d benzenesulfonate | C16H11DClNO5S | 366.79 |
2007(R) |
|
(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d benzenesulfonate | C16H11DClNO5S | 366.79 |
2007(S) |
|
(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d benzenesulfonate | C16H11DClNO5S | 366.79 |
2008 |
|
2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2008(R) |
|
(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2008(S) |
|
(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2009 |
|
2-amino-5-(2-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2009(R) |
|
(R)-2-amino-5-(2- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2009(S) |
|
(S)-2-amino-5-(2- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2010 |
|
2-amino-5-(3-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2010(R) |
|
(R)-2-amino-5-(3- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2010(S) |
|
(S)-2-amino-5-(3- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3ClNO5S | 382.83 |
2011 |
|
2-amino-5-(2,3- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2011(R) |
|
(R)-2-amino-5-(2,3- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2011(S) |
|
(S)-2-amino-5-(2,3- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2012 |
|
2-amino-5-(2,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2012(R) |
|
(R)-2-amino-5-(2,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2012(S) |
|
(S)-2-amino-5-(2,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2013 |
|
2-amino-5-(2,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2013(R) |
|
(R)-2-amino-5-(2,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2014(S) |
|
(S)-2-amino-5-(2,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2014 |
|
2-amino-5-(3,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2014(R) |
|
(R)-2-amino-5-(3,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2014(S) |
|
(S)-2-amino-5-(3,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2015 |
|
2-amino-5-(3,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2015(R) |
|
(R)-2-amino-5-(3,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2015(S) |
|
(S)-2-amino-5-(3,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3Cl2NO5S | 417.27 |
2016 |
|
methyl 3-(5-amino-3-oxo-4- (((phenylmethyl-d2) sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d) benzoate | C19H14D3NO7S | 406.42 |
2016(R) |
|
methyl (R)-3-(5-amino-3- oxo-4-(((phenylmethyl-d2) sulfonyl)oxy)-2,3-dihydro- furan-2-yl-2-d) benzoate | C19H14D3NO7S | 406.42 |
2016(S) |
|
methyl (S)-3-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d) benzoate | C19H14D3NO7S | 406.42 |
2017 |
|
methyl 4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H14D3NO7S | 406.42 |
2017(R) |
|
methyl (R)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H14D3NO7S | 406.42 |
2017(S) |
|
methyl (S)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H14D3NO7S | 406.42 |
2018 |
|
methyl 4-(5-amino-3-oxo-4- (((phenylmethyl-d2) sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoate | C19H13D3FNO7S | 424.41 |
2018(R) |
|
methyl (R)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoate | C19H13D3FNO7S | 424.41 |
2018(S) |
|
methyl (S)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoate | C19H13D3FNO7S | 424.41 |
2019 |
|
ethyl 4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C20H16D3NO7S | 420.45 |
2019(R) |
|
ethyl (R)-4-(5-amino-3-oxo- 4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C20H16D3NO7S | 420.45 |
2019(S) |
|
ethyl (S)-4-(5-amino-3-oxo- 4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C20H16D3NO7S | 420.45 |
2020 |
|
5-(4-acetylphenyl)-2-amino- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C19H14D3NO6S | 390.42 |
2020(R) |
|
(R)-5-(4-acetylphenyl)-2- amino-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H14D3NO6S | 390.42 |
2020(S) |
|
(S)-5-(4-acetylphenyl)-2- amino-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H14D3NO6S | 390.42 |
2021 |
|
2-amino-5-(4- carbamoylphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H13D3N2O6S | 391.41 |
2021(R) |
|
(R)-2-amino-5-(4- carbamoylphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H13D3N2O6S | 391.41 |
2021(S) |
|
(S)-2-amino-5-(4- carbamoylphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H13D3N2O6S | 391.41 |
2022 |
|
4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoic acid-d | C18H11D4NO7S | 393.40 |
2022(R) |
|
(R)-4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoic acid-d | C18H11D4NO7S | 393.40 |
2022(S) |
|
(S)-4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoic acid-d | C18H11D4NO7S | 393.40 |
2023 |
|
sodium 4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C18H11D3NNaO7S | 414.38 |
2023(R) |
|
sodium (R)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C18H11D3NNaO7S | 414.38 |
2023(S) |
|
sodium (S)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C18H11D3NNaO7S | 414.38 |
2024 |
|
potassium 4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C18H11D3KNO7S | 430.49 |
2024(R) |
|
potassium (R)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C18H11D3KNO7S | 430.49 |
2024(S) |
|
potassium (S)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C18H11D3KNO7S | 430.49 |
2027 |
|
2-amino-5-(2-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2027(R) |
|
(R)-2-amino-5-(2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2027(S) |
|
(S)-2-amino-5-(2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2028 |
|
2-amino-5-(3-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2028(R) |
|
(R)-2-amino-5-(3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2028(S) |
|
(S)-2-amino-5-(3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2029 |
|
2-amino-5-(4-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2029(R) |
|
(R)-2-amino-5-(4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2029(S) |
|
(S)-2-amino-5-(4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3FNO5S | 366.38 |
2030 |
|
2-amino-5-(2,3- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO2S | 384.37 |
2030(R) |
|
(R)-2-amino-5-(2,3- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2030(S) |
|
(S)-2-amino-5-(2,3- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2031 |
|
2-amino-5-(2,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2031(R) |
|
(R)-2-amino-5-(2,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2031(S) |
|
(S)-2-amino-5-(2,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2032 |
|
2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2032(R) |
|
(R)-2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2032(S) |
|
(S)-2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2033 |
|
2-amino-5-(2,6- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2033(R) |
|
(R)-2-amino-5-(2,6- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2033(S) |
|
(S)-2-amino-5-(2,6- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2034 |
|
2-amino-5-(3,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2034(R) |
|
(R)-2-amino-5-(3,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2034(S) |
|
(S)-2-amino-5-(3,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2035 |
|
2-amino-5-(3,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2035(R) |
|
(R)-2-amino-5-(3,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2035(S) |
|
(S)-2-amino-5-(3,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F2NO5S | 384.37 |
2036 |
|
2-amino-5-(2- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2036(R) |
|
(R)-2-amino-5-(2- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2036(S) |
|
(S)-2-amino-5-(2- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2037 |
|
2-amino-5-(3- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2037(R) |
|
(R)-2-amino-5-(3- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2037(S) |
|
(S)-2-amino-5-(3- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2038 |
|
2-amino-5-(4- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2038(R) |
|
(R)-2-amino-5-(4- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2038(S) |
|
(S)-2-amino-5-(4- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO6S | 378.41 |
2039 |
|
2-amino-5-(2,3- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2039(R) |
|
(R)-2-amino-5-(2,3- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2039(S) |
|
(S)-2-amino-5-(2,3- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2040 |
|
2-amino-5-(2,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2040(R) |
|
(R)-2-amino-5-(2,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2040(S) |
|
(S)-2-amino-5-(2,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2041 |
|
2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2041(R) |
|
(R)-2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2041(S) |
|
(S)-2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2042 |
|
2-amino-5-(2,6- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2042(R) |
|
(R)-2-amino-5-(2,6- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2042(S) |
|
(S)-2-amino-5-(2,6- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2043 |
|
2-amino-5-(3,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2043(R) |
|
(R)-2-amino-5-(3,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2043(S) |
|
(S)-2-amino-5-(3,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2044 |
|
2-amino-5-(3,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2044(R) |
|
(R)-2-amino-5-(3,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2044(S) |
|
(S)-2-amino-5-(3,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C19H16D3NO7S | 408.44 |
2045 |
|
2-amino-5-(2-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2045(R) |
|
(R)-2-amino-5-(2- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2045(S) |
|
(S)-2-amino-5-(2- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2046 |
|
2-amino-5-(3-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2046(R) |
|
(R)-2-amino-5-(3- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2046(S) |
|
(S)-2-amino-5-(3- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2047 |
|
2-amino-5-(4-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2047(R) |
|
(R)-2-amino-5-(4- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2047(S) |
|
(S)-2-amino-5-(4- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H11D3BrNO5S | 427.28 |
2048 |
|
2-amino-5-(2-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2048(R) |
|
(R)-2-amino-5-(2-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2048(S) |
|
(S)-2-amino-5-(2-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2049 |
|
2-amino-5-(2-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2049(R) |
|
(R)-2-amino-5-(2-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2049(S) |
|
(S)-2-amino-5-(2-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2050 |
|
2-amino-5-(2-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2050(R) |
|
(R)-2-amino-5-(2-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2050(S) |
|
(S)-2-amino-5-(2-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2051 |
|
2-amino-5-(2-chloro-6- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2051(R) |
|
(R)-2-amino-5-(2-chloro-6- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2051(S) |
|
(S)-2-amino-5-(2-chloro-6- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2052 |
|
2-amino-5-(3-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2052(R) |
|
(R)-2-amino-5-(3-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2052(S) |
|
(S)-2-amino-5-(3-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2053 |
|
2-amino-5-(3-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2053(R) |
|
(R)-2-amino-5-(3-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2053(S) |
|
(S)-2-amino-5-(3-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2054 |
|
2-amino-5-(3-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2054(R) |
|
(R)-2-amino-5-(3-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2054(S) |
|
(S)-2-amino-5-(3-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2055 |
|
2-amino-5-(5-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2055(R) |
|
(R)-2-amino-5-(5-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2055(S) |
|
(S)-2-amino-5-(5-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2056 |
|
2-amino-5-(4-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2056(R) |
|
(R)-2-amino-5-(4-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2056(S) |
|
(S)-2-amino-5-(4-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2057 |
|
2-amino-5-(4-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2057(R) |
|
(R)-2-amino-5-(4-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2057(S) |
|
(S)-2-amino-5-(4-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3ClFNO5S | 400.82 |
2058 |
|
2-amino-4-oxo-5-(o-tolyl)- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2058(R) |
|
(R)-2-amino-4-oxo-5-(o- tolyl)-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2058(S) |
|
(S)-2-amino-4-oxo-5-(o- tolyl)-4,5-dihydofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2059 |
|
2-amino-4-oxo-5-(m-tolyl)- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2059(R) |
|
(R)-2-amino-4-oxo-5-(m- tolyl)-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2059(S) |
|
(S)-2-amino-4-oxo-5-(m- tolyl)-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2060 |
|
2-amino-4-oxo-5-(p-tolyl)- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2060(R) |
|
(R)-2-amino-4-oxo-5-(p- tolyl)-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2060(S) |
|
(S)-2-amino-4-oxo-5-(p- tolyl)-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C18H14D3NO5S | 362.41 |
2061 |
|
2-amino-5-(3-cyanophenyl)- 4-oxo-4,5-dihydrofuran-5-d phenylmethanesulfonate-d2 | C18H11D3N2O5S | 373.40 |
2061(R) |
|
(R)-2-amino-5-(3- cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3N2O5S | 373.40 |
2061(S) |
|
(S)-2-amino-5-(3- cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3N2O5S | 373.40 |
2062 |
|
2-amino-5-(4-cyanophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d phenylmethanesulfonate-d2 | C18H11D3N2O5S | 373.40 |
2062(R) |
|
(R)-2-amino-5-(4- cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3N2O5S | 373.40 |
2062(S) |
|
(S)-2-amino-5-(4- cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3N2O5S | 373.40 |
2063 |
|
2-amino-4-oxo-5-phenyl-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H12D3NO5S | 348.39 |
2063(R) |
|
(R)-2-amino-4-oxo-5-phenyl- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H12D3NO5S | 348.39 |
2063(S) |
|
(S)-2-amino-4-oxo-5-phenyl- 4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H12D3NO5S | 348.39 |
2064 |
|
2-amino-4-oxo-5-(2- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2064(R) |
|
(R)-2-amino-4-oxo-5-(2- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2064(S) |
|
(S)-2-amino-4-oxo-5-(2- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2065 |
|
2-amino-4-oxo-5-(3- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2065(R) |
|
(R)-2-amino-4-oxo-5-(3- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2065(S) |
|
(S)-2-amino-4-oxo-5-(3- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2066 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2066(R) |
|
(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2066(S) |
|
(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D3F3NO5S | 416.39 |
2067 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (4- fluorophenyl) methanesulfonate-d2 | C18H10D3F4NO5S | 434.38 |
2067(R) |
|
(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (4-fluorophenyl) methanesulfonate-d2 | C18H10D3F4NO5S | 434.38 |
2067(S) |
|
(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (4- fluorophenyl) methanesulfonate-d2 | C18H10D3F4NO5S | 434.38 |
2068 |
|
methyl 4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H13D3FNO7S | 424.41 |
2068(R) |
|
methyl (R)-4-(5-amino-4- ((((4-fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H13D3FNO7S | 424.41 |
2068(S) |
|
methyl (S)-4-(5-amino-4- ((((4-fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H13D3FNO7S | 424.41 |
2069 |
|
ethyl 4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoate | C20H15D3FNO7S | 438.44 |
2069(R) |
|
ethyl (R)-4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoate | C20H15D3FNO7S | 438.44 |
2069(S) |
|
ethyl (S)-4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoate | C20H15D3FNO7S | 438.44 |
2070 |
|
4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoic acid-d | C18H10D4FNO7S | 411.39 |
2070(R) |
|
(R)-4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoic acid-d | C18H10D4FNO7S | 411.39 |
2070(S) |
|
(S)-4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoic acid-d | C18H10D4FNO7S | 411.39 |
2071 |
|
methyl 4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydofuran-2-yl-2-d)-2- fluorobenzoate | C19H12D3F2NO7S | 442.40 |
2071(R) |
|
methyl (R)-4-(5-amino-4- ((((4-fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoate | C19H12D3F2NO7S | 442.40 |
2071(S) |
|
methyl (S)-4-(5-amino-4- ((((4-fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoate | C19H12D3F2NO7S | 442.40 |
2072 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18H6D8F3NO5S | 421.42 |
2072(R) |
|
(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18H6D8F3NO5S | 421.42 |
2072(S) |
|
(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18H6D8F3NO5S | 421.42 |
2073 |
|
methyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H9D8NO7S | 411.45 |
2073(R) |
|
methyl (R)-4-(5-amino-3- oxo-4-((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H9D8NO7S | 411.45 |
2073(S) |
|
methyl (S)-4-(5-amino-3- oxo-4-((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C19H9D8NO7S | 411.45 |
2074 |
|
ethyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C20H11D8NO7S | 425.48 |
2074(R) |
|
ethyl (R)-4-(5-amino-3-oxo- 4-((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate | C20H11D8NO7S | 425.48 |
2074(S) |
|
ethyl (S)-4-(5-amino-3-oxo- 4-((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydofuran-2-yl-2- d)benzoate | C20H11D8NO7S | 425.48 |
2075 |
|
4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoic acid-d | C18H6D9NO7S | 398.43 |
2075(R) |
|
(R)-4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuan-2-yl-2- d)benzoic acid-d | C18H6D9NO7S | 398.43 |
2075(S) |
|
(S)-4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydofuran-2-yl-2- d)benzoic acid-d | C18H6D9NO7S | 398.43 |
2076 |
|
methyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoate | C19H8D8FNO7S | 429.44 |
2076(R) |
|
methyl (R)-4-(5-amino-3- oxo-4-((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoate | C19H8D8FNO7S | 429.44 |
2076(S) |
|
methyl (S)-4-(5-amino-3- oxo-4-((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoate | C19H8D8FNO7S | 429.44 |
2077 |
|
2-amino-5- (benzo[d][1,3]dioxol-5-yl)-4- oxo-4,5-dihydofuran-3-yl-5- d phenylmethanesulfonate-d2 | C18H12D3NO7S | 392.40 |
2077(R) |
|
(R)-2-amino-5- (benzo[d][1,3]dioxol-5-yl)-4- oxo-4,5-dihydrofuran-3-yl-5- d phenylmethanesulfonate-d2 | C18H12D3NO7S | 392.40 |
2077(S) |
|
(S)-2-amino-5- (benzo[d][1,3]dioxol-5-yl)-4- oxo-4,5-dihydrofuran-3-yl-5- d phenylmethanesulfonate-d2 | C18H12D3NO7S | 392.40 |
2078 |
|
2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol- 5-yl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H10D3F2NO7S | 428.38 |
2078(R) |
|
(R)-2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol- 5-yl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H10D3F2NO7S | 428.38 |
2078(S) |
|
(S)-2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol- 5-yl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H10D3F2NO7S | 428.38 |
2079 |
|
methyl 2-(4-(5-amino-3-oxo- 4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)phenyl)acetate-d2 | C20H14D5NO7S | 422.46 |
2079(R) |
|
methyl (R)-2-(4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)phenyl)acetate-d2 | C20H14D5NO7S | 422.46 |
2079(S) |
|
methyl (S)-2-(4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)phenyl)acetate-d2 | C20H14D5NO7S | 422.46 |
2080 |
|
2-amino-5-(4-(carbamoyl- d2)phenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H11D5N2O6S | 393.42 |
2080(R) |
|
(R)-2-amino-5-(4- (carbamoyl-d2)phenyl)-4- oxo-4,5-dihydrofuran-3-yl-5- d phenylmethanesulfonate-d2 | C18H11D5N2O6S | 393.42 |
2080(S) |
|
(S)-2-amino-5-(4- (carbamoyl-d2)phenyl)-4- oxo-4,5-dihydrofuran-3-yl-5- d phenylmethanesulfonate-d2 | C18H11D5N2O6S | 393.42 |
2081 |
|
2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3- yl)-4,5-dihydofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F3N2O5S | 417.37 |
2081(R) |
|
(R)-2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3- yl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F3N2O5S | 417.37 |
2081(S) |
|
(S)-2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3- yl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C17H10D3F3N2O5S | 417.37 |
2082 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydofuran-3-yl-5-d (4- chlorophenyl) methanesulfonate-d2 | C18H10D3ClF3NO5S | 450.83 |
2082(R) |
|
(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (4- chlorophenyl) methanesulfonate-d2 | C18H10D3ClF3NO5S | 450.83 |
2082(S) |
|
(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (4-chlorophenyl) methanesulfonate-d2 | C18H10D3ClF3NO5S | 450.83 |
2083 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (4- (trifluoromethyl)phenyl) methanesulfonate-d2 | C19H10D3F6NO5S | 484.38 |
2083(R) |
|
(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (4- (trifluoromethyl)phenyl) methanesulfonate-d2 | C19H10D3F6NO5S | 484.38 |
2084 |
|
2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H12D2F3NO5S | 415.38 |
2085 |
|
2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H9D5F3NO5S | 418.40 |
2085(R) |
|
(R)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H9D5F3NO5S | 418.40 |
2085(S) |
|
(S)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H9D5F3NO5S | 418.40 |
2086 |
|
2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (phenyl- d5)methanesulfonate | C18H7D7F3NO5S | 420.41 |
2087 |
|
2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18H4D10F3NO5S | 423.43 |
2087(R) |
|
(R)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18H4D10F3NO5S | 423.43 |
2087(S) |
|
(S)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18H4D10F3NO5S | 423.43 |
2088 |
|
2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl phenylmethanesulfonate | C18H8D6F3NO5S | 419.40 |
2089 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H7D7F3NO5S | 420.41 |
2089(R) |
|
(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H7D7F3NO5S | 420.41 |
2089(S) |
|
(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H7D7F3NO5S | 420.41 |
2090 |
|
2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H5D9F3NO5S | 422.42 |
2091(R) |
|
(R)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H5D9F3NO5S | 422.42 |
2090(S) |
|
(S)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 | C18H5D9F3NO5S | 422.42 |
2091 |
|
2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl (phenyl- d5)methanesulfonate | C18H3D11F3NO5S | 424.43 |
2092 |
|
2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl (phenyl- d5)methanesulfonate-d2 | C18H2D12F3NO5S | 425.44 |
2092(R) |
|
(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18H2D12F3NO5S | 425.44 |
2092(S) |
|
(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18H2D12F3NO5S | 425.44 |
2093 |
|
2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18D14F3NO5S | 427.45 |
2093(R) |
|
(R)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18D14F3NO5S | 427.45 |
2093(S) |
|
(S)-2-amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5- dihydrofuran-3-yl-5-d (phenyl-d5) methanesulfonate-d2 | C18D14F3NO5S | 427.45 |
- 1. AIHARA, A., C. K. HUANG, M. J. OLSEN, Q. LIN, W. CHUNG, Q. TANG, X. DONG AND J. R. WANDS (2014). “A cell-surface beta-hydroxylase is a biomarker and therapeutic target for hepatocellular carcinoma.” Hepatology 60(4): 1302-1313.
- 2. BORGAS, D. L., J. S. GAO, M. TONG AND S. M. DE LA MONTE (2015). “Potential Role of Phosphorylation as a Regulator of Aspartyl-(asparaginyl)-beta-hydroxylase: Relevance to Infiltrative Spread of Human Hepatocellular Carcinoma.” Liver Cancer 4(3): 139-153.
- 3. BORGAS, D. L., J. S. GAO, M. TONG, N. ROPER AND S. M. DE LA MONTE (2015). “Regulation of Aspartyl-(Asparaginyl)-beta-Hydroxylase Protein Expression and Function by Phosphorylation in Hepatocellular Carcinoma Cells.” J Nat Sci 1(4).
- 4. CANTARINI, M. C., S. M. DE LA MONTE, M. PANG, M. TONG, A. D'ERRICO, F. TREVISANI AND J. R. WANDS (2006). “Aspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms.” Hepatology 44(2): 446-457.
- 5. DINCHUK, J. E., R. J. FOCHT, J. A. KELLEY, N. L. HENDERSON, N. I. ZOLOTARJOVA, R. WYNN, N. T. NEFF, J. LINK, R. M. HUBER, T. C. BURN, M. J. RUPAR, M. R. CUNNINGHAM, B. H. SELLING, J. MA, A. A. STERN, G. F. HOLLIS, R. B. STEIN AND P. A. FRIEDMAN (2002). “Absence of post-translational aspartyl beta-hydroxylation of epidermal growth factor domains in mice leads to developmental defects and an increased incidence of intestinal neoplasia.” J Biol Chem 277(15): 12970-12977.
- 6. DRAKENBERG, T., P. FERNLUND, P. ROEPSTORFF AND J. STENFLO (1983). “beta-Hydroxyaspartic acid in vitamin K-dependent protein C.” Proc Natl Acad Sci USA 80(7): 1802-1806.
- 7. EL ASMAR, Z., J. TERRAND, M. JENTY, L. HOST, M. MLIH, A. ZERR, H. JUSTINIANO, R. L. MATZ, C. BOUDIER, E. SCHOLLER, J. M. GARNIER, D. BERTACCINI, D. THIERSE, C. SCHAEFFER, A. VAN DORSSELAER, J. HERZ, V. BRUBAN AND P. BOUCHER (2016). “Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation.” J Biol Chem 291(10): 5116-5127.
- 8. FURLER, R. L., D. F. NIXON, C. A. BRANTNER, A. POPRATILOFF AND C. H. UITTENBOGAART (2018). “TGF-beta Sustains Tumor Progression through Biochemical and Mechanical Signal Transduction.” Cancers (Basel) 10(6).
- 9. GUNDOGAN, F., G. ELWOOD, D. GRECO, L. P. RUBIN, H. PINAR, R. I. CARLSON, J. R. WANDS AND S. M. DE LA MONTE (2007). “Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation: Relevance to early pregnancy loss.” Hum Pathol 38(1): 50-59.
- 10. IWAGAMI, Y., S. CASULLI, K. NAGAOKA, M. KIM, R. I. CARLSON, K. OGAWA, M. S. LEBOWITZ, S. FULLER, B. BISWAS, S. STEWART, X. DONG, H. GHANBARI AND J. R. WANDS (2017). “Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma.” Heliyon 3(9): e00407.
- 11. LAVAISSIERE, L., S. JIA, M. NISHIYAMA, S. DE LA MONTE, A. M. STERN, J. R. WANDS AND P. A. FRIEDMAN (1996). “Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma.” J Clin Invest 98(6): 1313-1323.
- 12. NODA, T., M. SHIMODA, V. ORTIZ, A. E. SIRICA AND J. R. WANDS (2012). “Immunization with aspartate-beta-hydroxylase-loaded dendritic cells produces antitumor effects in a rat model of intrahepatic cholangiocarcinoma.” Hepatology 55(1): 86-97.
- 13. REVSKAYA, E., Z. JIANG, A. MORGENSTERN, F. BRUCHERTSEIFER, M. SESAY, S. WALKER, S. FULLER, M. S. LEBOWITZ, C. GRAVEKAMP, H. A. GHANBARI AND E. DADACHOVA (2017). “A Radiolabeled Fully Human Antibody to Human Aspartyl (Asparaginyl) beta-Hydroxylase Is a Promising Agent for Imaging and Therapy of Metastatic Breast Cancer.” Cancer Biother Radiopharm 32(2): 57-65.
- 14. TONG, M., J. S. GAO, D. BORGAS AND S. M. DE LA MONTE (2013). “Phosphorylation Modulates Aspartyl-(Asparaginyl)-beta Hydroxylase Protein Expression, Catalytic Activity and Migration in Human Immature Neuronal Cerebellar Cells.” Cell Biol (Henderson, Nev.) 6(2).
- 15. WU, G., Z. MA, Y. CHENG, W. HU, C. DENG, S. JIANG, T. LI, F. CHEN AND Y. YANG (2018). “Targeting Gas6/TAM in cancer cells and tumor microenvironment.” Mol Cancer 17(1): 20.
- 16. YANG, H., K. SONG, T. XUE, X. P. XUE, T. HUYAN, W. WANG AND H. WANG (2010). “The distribution and expression profiles of human Aspartyl/Asparaginyl beta-hydroxylase in tumor cell lines and human tissues.” Oncol Rep 24(5): 1257-1264.
- 17. YEUNG, Y. A., A. H. FINNEY, I. A. KOYRAKH, M. S. LEBOWITZ, H. A. GHANBARI, J. R. WANDS AND K. D. WITTRUP (2007). “Isolation and characterization of human antibodies targeting human aspartyl (asparaginyl) beta-hydroxylase.” Hum Antibodies 16(3-4): 163-176.
- 18. DAHN, H., LAWENDEL, J. S., HOEGGER, E. F. ET AL. (1954) “Ober eine neue Herstellung aromatisch substituierter Reduktone.” Experientia 10: 245.
- 19. PDB ID 5JZZ: McDonough, M. A., Pfeffer, I., Munzel, M. (2016) Aspartyl/Asparaginyl beta-hydroxylase (AspH)oxygenase and TPR domains in complex with manganese, N-oxalylglycine and cyclic peptide substrate mimic of factor X. DOI: 10.2210/pdb5JZZ/pdb. Deposited as PDB ID 5JZZ on 2016 May 16, Released on 2017 Jun. 6.
- 20. TIMMINS, G. S. (2014) “Deuterated drugs: where are we now?” Expert Opin. Ther. Patents 24(10):1067-1075.
- U.S. Pat. No. 9,771,356.
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US17/119,602 US11897857B2 (en) | 2019-02-15 | 2020-12-11 | Isotopically-stabilized tetronimide compounds |
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